Conservative Oxygen Therapy during Mechanical Ventilation in the ICU.

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.).

Fragmentation of care between intensive and primary care settings and opportunities for improvement.

PURPOSE: To explore the gaps in care provided across the transitions from the intensive care unit (ICU) to primary care, in order to improve post-ICU care. METHODS: Semistructured interviews with three participant groups: intensivists, general practitioners (GPs) and patients and carers with framework analysis of textual data were used to investigate experiences of transitions of care post-ICU. Participants were purposively sampled for diversity. Eligible patients were adults, mechanically ventilated for >24 hours, with access to a video-enabled device. Exclusion criteria were non-English speaking and any cognitive/neurological limitation precluding interview participation. RESULTS: A total of 46 interviews (15 patients, 8 caregivers, 15 intensivists and 8 GPs) were completed. Eight themes were identified, and categorised into three healthcare tiers. Tier 1, health system factors: (1) fragmentation of care; (2) communication gaps; (3) limited awareness and recognition of issues beyond the ICU; (4) lack of a specialised ICU follow-up pathway; Tier 2, clinician factors: (5) relationships among ICU, hospitals, GPs and patients and carers; (6) need for clinician role definition and clarity in ICU follow-up; Tier 3, patient and carer factors: (7) patient autonomy and self-actualisation and (8) the evolving caregiver role. A conceptual model was developed, highlighting bidirectional feedback loops between hospital and primary care. CONCLUSION: This study identified gaps in care between ICU discharge and reintegration with primary care from the lived experience of patients, caregivers, intensivists and GPs. These data provide foci for future interventional research to improve the integration of care for this vulnerable and underserved cohort.

The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

Extended Daily Dialysis Versus Continuous Renal Replacement Therapy for Acute Kidney Injury: A Meta-analysis.

BACKGROUND: Extended daily dialysis (EDD) has been suggested as an effective renal replacement therapy for acute kidney injury. However, results from studies comparing EDD to continuous renal replacement therapy (CRRT) are inconclusive. STUDY DESIGN: A systematic review and meta-analysis was performed by searching in MEDLINE, EMBASE, the Cochrane Library, Google Scholar, and a Chinese database (SinsoMed). SETTING & POPULATION: Patients with acute kidney injury. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials (RCTs) and observational studies were included. EDD was defined as extended hemodialysis or hemodiafiltration for more than 6 but less than 24 hours per session using a conventional hemodialysis machine. INTERVENTION: Renal replacement therapy comparing EDD with CRRT. OUTCOMES: Mortality, kidney recovery, and fluid removal. RESULTS: We included 17 studies from 2000 to 2014: 7 RCTs and 10 observational studies involving 533 and 675 patients, respectively. Meta-analysis of RCTs showed no difference in mortality rates between EDD and CRRT (relative risk, 0.90; 95% CI, 0.74-1.11; P=0.3). However, EDD was associated with lower mortality risk compared with CRRT in observational studies (relative risk, 0.86; 95% CI, 0.74-1.00; P=0.05). There was no evidence of heterogeneity in RCTs (I(2)=0%) or observational studies (I(2)=15%). In both RCTs and observational studies, there were no significant differences in recovery of kidney function, fluid removal, or days in the intensive care unit, and EDD showed similar biochemical efficacy to CRRT during treatment (serum urea, serum creatinine, and serum phosphate). LIMITATIONS: The survival benefit of EDD is dependent on only observational studies and might have been affected by allocation or selection bias. CONCLUSIONS: EDD is associated with similar outcomes to CRRT in RCTs. The finding that EDD is associated with a lower mortality rate relies on data from observational studies, which are potentially subject to allocation or selection bias, making further high-quality RCTs desirable.

Clinician- and Patient-Identified Solutions to Reduce the Fragmentation of Post-ICU Care in Australia.

BACKGROUND: Critical care survivors experience multiple care transitions, with no formal follow-up care pathway. RESEARCH QUESTION: What are the potential solutions to improve the communication between treating teams and integration of care following an ICU admission, from the perspective of patients, their caregivers, intensivists, and general practitioners (GPs) from diverse socioeconomic areas? STUDY DESIGN AND METHODS: This study included a qualitative design using semi-structured interviews with intensivists, GPs, and patients and caregivers. Framework analysis was used to analyze data and to identify solutions to improve the integration of care following hospital discharge. Patients were previously mechanically ventilated for > 24 h in the ICU and had access to a video-enabled device. Clinicians were recruited from hospital networks and a state-wide GP network. RESULTS: Forty-six interviews with clinicians, patients, and caregivers were completed (15 intensivists, eight GPs, 15 patients, and eight caregivers). Three higher level feedback loops were identified that comprised 10 themes. Feedback loop 1 was an ICU and primary care collaboration. It included the following: (1) developing collaborative relationships between the ICU and primary care; (2) providing interprofessional education and resources to support primary care; and (3) improving role clarity for patient follow-up care. Feedback loop 2 was developing mechanisms for improved communication across the care continuum. It included: (4) timely, concise information-sharing with primary care on post-ICU recovery; (5) survivorship-focused information-sharing across the continuum of care; (6) empowering patients and caregivers in self-management; and (7) creation of a care coordinator role for survivors. Feedback loop 3 was learning from post-ICU outcomes to improve future care. It included: (8) developing comprehensive post-ICU care pathways; (9) enhancing support for patients following a hospital stay; and (10) integration of post-ICU outcomes within the ICU to improve clinician morale and understanding. INTERPRETATION: Practical solutions to enhance the quality of survivorship for critical care survivors and their caregivers were identified. These themes are mapped to a novel conceptual model that includes key feedback loops for health system improvements and foci for future interventional trials to improve ICU survivorship outcomes.

Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.

BACKGROUND: To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear. METHODS/DESIGN: The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan. DISCUSSION: This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.

Protocol summary and statistical analysis plan for the intensive care unit randomised trial comparing two approaches to oxygen therapy (ICU-ROX).

BACKGROUND: The balance of risks and benefits of conservative v standard care oxygen strategies for patients who are invasively ventilated in the intensive care unit (ICU) is uncertain. OBJECTIVE: To describe the study protocol and statistical analysis plan for the ICU randomised trial comparing two approaches to oxygen therapy (ICU-ROX). DESIGN, SETTING AND PARTICIPANTS: Protocol for a multicentre, randomised, participant and outcome assessor-blinded, standard care-controlled, parallel-group, two-sided superiority trial to be conducted in up to 22 ICUs in Australia and New Zealand. 1000 adults who are mechanically ventilated in the ICU and expected to remain ventilated beyond the day after recruitment will be randomly assigned to conservative oxygen therapy or standard care in a 1:1 ratio. ICU-ROX began with an internal pilot phase in September 2015. It is anticipated that recruitment will be completed in 2018. MAIN OUTCOME MEASURES: The primary endpoint will be alive, ventilator-free days to Day 28. Secondary outcomes include 90- and 180-day all-cause mortality, survival time to 180 days, and quality of life and cognitive function at 180 days. All analyses will be conducted on an intentionto- treat basis. RESULTS AND CONCLUSIONS: ICU-ROX will compare the effect of conservative v standard oxygen therapy in critically ill mechanically ventilated adults who are expected to be ventilated beyond the day after recruitment on ventilatorfree days to Day 28. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTRN 12615000957594).