Making ICU Research Happen: a Qualitative Descriptive Study About the Role of the Research Nurse in New Zealand Level III Intensive Care Units

This study explored the role of the research nurse in New Zealand (NZ) Level III intensive care units (ICU). Little was known about this role in NZ prior to this study. A qualitative, descriptive approach, using semi-structured interviews was used. The study was conducted in six Level III ICUs throughout NZ, who employed a research nurse. Interviews were conducted with research nurses (n = 11), the doctors they work with (principal investigators) (n = 6) and nurse managers (n = 6) for the ICUs, and the findings were triangulated. The views across all ICUs and stakeholders were generally similar, with differences only being in some operational areas. This study found that the primary role of the research nurse was trial management, where they coordinated all elements of trial conduct. Almost half of the research nurses were also involved in trial design through their positions on management committees. Research nurses also played a vital role in patient and trial advocacy, and they bridged the knowledge gap by bringing research to staff nurses, patients and their families. The issue of consent for clinical trials in the ICU setting was significant, as this was a process which research nurses were very involved in. Consenting patients was a shared responsibility of research nurses and doctors. There was a perception that research nurses were senior nurses, but not necessarily because of their role in research. The majority of research nurses reported to a nursing line manager, and also had an informal accountability to the principal investigator (PI). Research nurses and PIs worked closely in the pursuit of rigorous research for ICU patients, and research nurses were highly regarded by PIs. This study provides clarity about the research nurse‟s role and showcases their key contribution in ensuring that NZ ICUs undertake high quality research, thus contributing to potential improvements for future patients‟ outcomes

How big is your bubble? : characteristics of self-isolating household units ('bubbles') during the COVID-19 Alert Level 4 period in New Zealand : a cross-sectional survey

Objective To characterise the self-isolating household units (bubbles) during the COVID-19 Alert Level 4 lockdown in New Zealand. Design, setting and participants In this cross-sectional study, an online survey was distributed to a convenience sample via Facebook advertising and the Medical Research Institute of New Zealand's social media platforms and mailing list. Respondents were able to share a link to the survey via their own social media platforms and by email. Results were collected over 6 days during Alert Level 4 from respondents living in New Zealand, aged 16 years and over. Main outcomes measures The primary outcome was the mean size of a self-isolating household unit or bubble. Secondary outcomes included the mean number of households in each bubble, the proportion of bubbles containing essential workers and/or vulnerable people, and the mean number of times the home was left each week. Results 14 876 surveys were included in the analysis. The mean (SD) bubble size was 3.58 (4.63) people, with mean (SD) number of households 1.26 (0.77). The proportion of bubbles containing one or more essential workers, or one or more vulnerable persons was 45.3% and 42.1%, respectively. The mean number of times individual bubble members left their home in the previous week was 12.9 (12.4). Bubbles that contained at least one vulnerable individual had fewer outings over the previous week compared with bubbles that did not contain a vulnerable person. The bubble sizes were similar by respondent ethnicity. Conclusion In this New Zealand convenience sample, bubble sizes were small, mostly limited to one household, and a high proportion contained essential workers and/or vulnerable people. Understanding these characteristics from a country which achieved a low COVID-19 infection rate may help inform public health interventions during this and future pandemics

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with sepsis in the intensive care unit (Mega-ROX Sepsis)

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial. Design, setting, and participants: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of patients discharged home. Results and conclusions: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with nonhypoxic ischaemic acute brain injuries and conditions in the intensive care unit (Mega-ROX Brains)

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults who have nonhypoxic ischaemic encephalopathy acute brain injuries and conditions and are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Brains trial. Design, setting, and participants: Mega-ROX Brains is an international randomised clinical trial, which will be conducted within an overarching 40,000-participant, registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol between 7500 and 9500 participants with nonhypoxic ischaemic encephalopathy acute brain injuries and conditions who are receiving unplanned invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 d from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home. Results and conclusions: Mega-ROX Brains will compare the effect of conservative vs. liberal oxygen therapy regimens on 90-day in-hospital mortality in adults in the ICU with acute brain injuries and conditions. The protocol and planned analyses are reported here to mitigate analysis bias. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976)

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Oxygen management in New Zealand and Australian intensive care units: A knowledge translation study

Background: Knowledge translation literature shows a delay between publication and uptake of research findings into clinical practice. There is uncertainty about whether this delay exists in the intensive care unit (ICU) context and whether participation in research influences changes in clinical practice. Knowing whether ICU participation in research increases the likelihood of research findings being incorporated into clinical care is important to funders, researchers and patients. Aim: To investigate the effects of participating in the Intensive Care Unit Randomised Trial Comparing Two Approaches to Oxygen therapy (ICU-ROX) randomised controlled trial on attitudes and practices in relation to ICU oxygen therapy. Methods: The research question was examined using three different methods: a survey, an inception cohort study, and a retrospective cohort study. The practitioner attitudes survey and inception cohort study were conducted before ICU-ROX started, after ICU-ROX finished but before the results were known, and, finally, after publication of the ICU-ROX results. The retrospective cohort study (using the Australian and New Zealand ICU adult patient database) compared data from 48 weeks before and 48 weeks after publication of the ICU-ROX trial. Results: Practitioner attitudes survey: Responses were received from 112 specialist doctors and 153 ICU nurses from 11 ICU-ROX and 11 non-ICU-ROX sites. Before the ICU-ROX trial was conducted, respondents from ICU-ROX trial sites and those from non-ICU-ROX trial sites were similarly likely to indicate they would use a fraction of inspired oxygen (FIO2) of 0.21, in a ventilated patient with peripheral oxygen saturations (SpO2) of 91-96%. However, after participation in the ICU-ROX trial, and before the trial results were known, ICU-ROX trial site respondents were significantly more likely than their non-ICU-ROX trial site counterparts to state they would use an FIO2 of 0.21 in a patient with an SpO2 of 91-96%. The differences in all patient admission categories, except the ‘other ICU patients’ category, persisted after the ICU-ROX trial was published. Nurses were generally less likely to report they would use an FIO2 of 0.21 in a ventilated patient than doctors. Following ICU-ROX publication, 41.1% of the doctors compared to 13.6% of the nurses knew the ICU-ROX results (P Inception cohort study: Data were analysed from 650 patients from 11 ICU-ROX and 11 non-ICU-ROX sites. ICU-ROX site patients spent 8.2% of the time ventilated at FIO2 of 0.21, before ICU-ROX started, 7.7% after their participation in the ICU-ROX trial and 7.1% of the time after ICU-ROX publication, a change over time was not statistically significant. For the non-ICU-ROX site patients, time spent ventilated at FIO2 of 0.21 was 0.9% before ICU-ROX, 2.4% after ICU-ROX was conducted and 3.3% after publication. This change for non-ICU-ROX site patients after ICU-ROX publication was statistically significant (relative rate 3.63; 95% CI 1.39 to 9.47, P=0.01). Retrospective cohort study: The FIO2 from the arterial blood gas associated with the worst Acute Physiology and Chronic Health Evaluation III-J score in the first 24 hours of admission to ICU was analysed for 51,498 pre-publication admissions and 47,523 post-publication admissions from 15 ICU-ROX sites and 188 non-ICU-ROX sites. Although the average FIO2 values varied considerably from week to week, there was a statistically significant reduction in the average FIO2 over time in ICU-ROX sites (P=0.01) but not in non-ICU-ROX sites (P=0.49). Conclusion: Differences between attitudes of practitioners in relation to oxygen in ICU-ROX sites compared with non-ICU-ROX sites changed over time (before and after the ICU-ROX trial, and after publication of the results). Differences in oxygen therapy practice changes for ICU-ROX versus non-ICU-ROX sites shown in the inception cohort study and retrospective cohort study were small, and are unlikely to be clinically important. These studies did not demonstrate a consistent effect of participation in ICU-ROX on knowledge translation.</p

Conservative or liberal oxygen therapy in adults after cardiac arrest An individual-level patient data meta-analysis of randomised controlled trials

Aim: The effect of conservative versus liberal oxygen therapy on mortality rates in post cardiac arrest patients is uncertain. Methods: We undertook an individual patient data meta-analysis of patients randomised in clinical trials to conservative or liberal oxygen therapy after a cardiac arrest. The primary end point was mortality at last follow-up. Results: Individual level patient data were obtained from seven randomised clinical trials with a total of 429 trial participants included. Four trials enrolled patients in the pre-hospital period. Of these, two provided protocol-directed oxygen therapy for 60 min, one provided it until the patient was handed over to the emergency department staff, and one provided it for a total of 72 h or until the patient was extubated. Three trials enrolled patients after intensive care unit (ICU) admission and generally continued protocolised oxygen therapy for a longer period, often until ICU discharge. A total of 90 of 221 patients (40.7%) assigned to conservative oxygen therapy and 103 of 206 patients (50%) assigned to liberal oxygen therapy had died by this last point of followup; absolute difference; odds ratio (OR) adjusted for study only; 0.67; 95% CI 0.45 to 0.99; P = 0.045; adjusted OR, 0.58; 95% CI 0.35 to 0.96; P = 0.04. Conclusion: Conservative oxygen therapy was associated with a statistically significant reduction in mortality at last follow-up compared to liberal oxygen therapy but the certainty of available evidence was low or very low due to bias, imprecision, and indirectness. PROSPERO registration number: CRD42019138931.Peer reviewe

Randomised evaluation of active control of temperature versus ordinary temperature management (REACTOR) trial

Purpose: It is unknown whether protocols targeting systematic prevention and treatment of fever achieve lower mean body temperature than usual care in intensive care unit (ICU) patients. The objective of the Randomised Evaluation of Active Control of temperature vs. ORdinary temperature management trial was to confrm the feasibility of such a protocol with a view to conducting a larger trial. Methods: We randomly assigned 184 adults without acute brain pathologies who had a fever in the previous 12 h, and were expected to be ventilated beyond the calendar day after recruitment, to systematic prevention and treatment of fever or usual care. The primary outcome was mean body temperature in the ICU within 7 days of randomisation. Secondary outcomes included in-hospital mortality, ICU-free days and survival time censored at hospital discharge. Results: Compared with usual temperature management, active management signifcantly reduced mean temperature. In both groups, fever generally abated within 72 h. The mean temperature diference between groups was greatest in the frst 48 h, when it was generally in the order of 0.5 °C. Overall, 23 of 89 patients assigned to active management (25.8%) and 23 of 89 patients assigned to usual management (25.8%) died in hospital (odds ratio 1.0, 95% CI 0.51–1.96, P=1.0). There were no statistically signifcant diferences between groups in ICU-free days or survival to day 90. Conclusions: Active temperature management reduced body temperature compared with usual care; however, fever abated rapidly, even in patients assigned to usual care, and the magnitude of temperature separation was small.The REACTOR study was endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group and funded by the Health Research Council of New Zealand (16/488). The study was coordinated by the Medical Research Institute of New Zealand in New Zealand and the George Institute for Global Health in Australia. The Medical Research Institute of New Zealand is supported by Independent Research Organisation funding by the Health Research Council of New Zealan