Critical Care - Research Publications

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    A multicentre point prevalence study of delirium assessment and management in patients admitted to Australian and New Zealand intensive care units
    Ankravs, MJ ; Udy, AA ; Byrne, K ; Knowles, S ; Hammond, N ; Saxena, MK ; Reade, MC ; Bailey, M ; Bellomo, R ; Deane, AM (AUSTRALASIAN MED PUBL CO LTD, 2020-12)
    Objective: To characterise the assessment and management of delirium in patients admitted to intensive care units (ICUs) in Australia and New Zealand. Methods: We conducted a multicentre observational point prevalence study across 44 adult Australian and New Zealand ICUs. Data were extracted for all patients in the ICU in terms of assessment and treatment of delirium. ICU-level data were collected regarding the use of explicit protocols related to delirium. Results: We studied 627 patients, with 54% (336/627) having at least one delirium screening assessment performed. The Confusion Assessment Method for the ICU (CAM-ICU) was the most frequently used tool (88%, 296/336). Of patients assessed, 20% (68) were identified to have delirium. Eighteen per cent (111) of patients were administered a drug to manage delirium, with 41% (46) of those receiving a drug having no recorded assessment for delirium on that day. Of the drugs used to treat delirium, quetiapine was the most frequently administered. Physical restraints were applied to 8% (48/626) of patients, but only 17% (8/48) of such patients had been diagnosed with delirium. Most physically restrained patients either did not have delirium diagnosed (31%, 15/48) or had no formal assessment recorded (52%, 25/48) on that day. Conclusions: On the study day, more than 50% of patients had a delirium screening assessment performed, with 20% of screened patients deemed to have delirium. Drugs that are prescribed to treat delirium and physical restraints were frequently used in the absence of delirium or the formal assessment for its presence.
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    Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock The VITAMINS Randomized Clinical Trial
    Fujii, T ; Luethi, N ; Young, PJ ; Frei, DR ; Eastwood, GM ; French, CJ ; Deane, AM ; Shehabi, Y ; Hajjar, LA ; Oliveira, G ; Udy, AA ; Orford, N ; Edney, SJ ; Hunt, AL ; Judd, HL ; Bitker, L ; Cioccari, L ; Naorungroj, T ; Yanase, F ; Bates, S ; McGain, F ; Hudson, EP ; Al-Bassam, W ; Dwivedi, DB ; Peppin, C ; McCracken, P ; Orosz, J ; Bailey, M ; Bellomo, R ; French, CJ ; Deane, AM ; Hajjar, LA ; Oliveira, G ; Orford, N ; Shehabi, Y ; Udy, AA ; Young, PJ ; McCracken, P ; Board, J ; Martin, E ; Vallance, S ; Young, M ; Bellomo, R ; Eastwood, GM ; Cioccari, L ; Bitker, L ; Yanase, F ; Naorungroj, T ; Hessels, L ; Peck, L ; Young, H ; Percy, N ; Shepherd, K ; Peppin, C ; Dwivedi, DB ; Lukas, G ; Fazli, F ; Murfin, B ; Bates, S ; Morgan, R ; Marshall, F ; Tippett, A ; Towns, M ; Elderkin, T ; Bone, A ; Salerno, T ; Hudson, EP ; Barge, D ; Anstey, J ; Abdelhamid, YA ; Jelbart, B ; Byrne, K ; Tascone, B ; Doherty, S ; Beehre, N ; Hunt, A ; Judd, H ; Latimer-Bell, C ; Lawrence, C ; Robertson, Y ; Smellie, H ; Vucago, AM ; Bailey, M ; Fujii, T ; Howe, BD ; Luethi, N ; Murray, L ; Trapani, T (AMER MEDICAL ASSOC, 2020-02-04)
    IMPORTANCE: It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock. OBJECTIVE: To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019. INTERVENTIONS: Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days. MAIN OUTCOMES AND MEASURES: The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality. RESULTS: Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported. CONCLUSIONS AND RELEVANCE: In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03333278.
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    Conservative Oxygen Therapy during Mechanical Ventilation in the ICU
    Mackle, D ; Bellomo, MNR ; Bailey, M ; Beasley, R ; Deane, A ; Eastwood, G ; Finfer, S ; Freebairn, R ; King, V ; Linke, N ; Litton, E ; McArthur, C ; McGuinness, S ; Panwar, R ; Young, P (MASSACHUSETTS MEDICAL SOC, 2020-03-12)
    BACKGROUND: Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation). METHODS: We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28. RESULTS: The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of -0.3 days (95% confidence interval [CI], -2.1 to 1.6; P = 0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37). CONCLUSIONS: In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days. (Funded by the Health Research Council of New Zealand; ICU-ROX Australian and New Zealand Clinical Trials Registry number, ACTRN12615000957594.).
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    Conservative oxygen therapy for mechanically ventilated adults with suspected hypoxic ischaemic encephalopathy
    Young, P ; Mackle, D ; Bellomo, R ; Bailey, M ; Beasley, R ; Deane, A ; Eastwood, G ; Finfer, S ; Freebairn, R ; King, V ; Linke, N ; Litton, E ; McArthur, C ; McGuinness, S ; Panwar, R (SPRINGER, 2020-12)
    PURPOSE: Liberal use of oxygen may contribute to secondary brain injury in patients with hypoxic-ischaemic encephalopathy (HIE). However, there are limited data on the effect of different oxygen regimens on survival and neurological disability in HIE patients. METHODS: We undertook a post-hoc analysis of the 166 patients with suspected HIE enrolled in a trial comparing conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary endpoint for the current analysis was death or unfavourable neurological outcome at day 180. Key secondary outcomes were day 180 mortality, and cause-specific mortality. RESULTS: Patients with HIE allocated to conservative oxygen spent less time in the ICU with an SpO2 ≥ 97% (26 h [interquartile range (IQR) 13-45 vs. 35 h [IQR 19-70], absolute difference, 9 h; 95% CI - 21.4 to 3.4). A total of 43 of 78 patients (55.1%) assigned to conservative oxygen and 49 of 72 patients (68.1%) assigned to usual oxygen died or had an unfavourable neurological outcome at day 180; odds ratio 0.58; 95% CI 0.3-1.12; P = 0.1 adjusted odds ratio 0.54; 95% CI 0.23-1.26; P = 0.15. A total of 37 of 86 patients (43%) assigned to conservative oxygen and 46 of 78 (59%) assigned to usual oxygen had died by day 180; odds ratio 0.53; 95% CI 0.28-0.98; P = 0.04; adjusted odds ratio 0.56; 95% CI 0.25-1.23; P = 0.15. Cause-specific mortality was similar by treatment group. CONCLUSIONS: Conservative oxygen therapy was not associated with a statistically significant reduction in death or unfavourable neurological outcomes at day 180. The potential for important benefit or harm from conservative oxygen therapy in HIE patients is not excluded by these data.
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    Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX)
    Young, P ; Mackle, D ; Bellomo, R ; Bailey, M ; Beasley, R ; Deane, A ; Eastwood, G ; Finfer, S ; Freebairn, R ; King, V ; Linke, N ; Litton, E ; McArthur, C ; McGuinness, S ; Panwar, R (SPRINGER, 2020-01)
    PURPOSE: Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. METHODS: We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. RESULTS: Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO2 ≥ 97% (23.5 h [interquartile range (IQR) 8-70] vs. 47 h [IQR 11-93], absolute difference, 23 h; 95% CI 8-38), and more time receiving an FiO2 of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1-79] vs. 0 h [IQR 0-10], absolute difference, 20 h; 95% CI 14-26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI - 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy. CONCLUSIONS: Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group. CLINICAL TRIALS REGISTRY: ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594.