Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial.

RATIONALE: There are no randomized controlled trials comparing different oxygenation targets for intensive care unit (ICU) patients. OBJECTIVES: To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation (IMV). METHODS: At four multidisciplinary ICUs, 103 adult patients deemed likely to require IMV for greater than or equal to 24 hours were randomly allocated to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88-92% (n = 52) or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% (n = 51). MEASUREMENTS AND MAIN RESULTS: The mean area under the curve and 95% confidence interval (CI) for SpO2 (93.4% [92.9-93.9%] vs. 97% [96.5-97.5%]), SaO2 (93.5% [93.1-94%] vs. 96.8% [96.3-97.3%]), PaO2 (70 [68-73] mm Hg vs. 92 [89-96] mm Hg), and FiO2 (0.26 [0.25-0.28] vs. 0.36 [0.34-0.39) in the conservative versus liberal oxygenation arm were significantly different (P < 0.0001 for all). There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality. The percentage time spent with SpO2 less than 88% in conservative versus liberal arm was 1% versus 0.3% (P = 0.03), and percentage time spent with SpO2 greater than 98% in conservative versus liberal arm was 4% versus 22% (P < 0.001). The adjusted hazard ratio for 90-day mortality in the conservative arm was 0.77 (95% CI, 0.40-1.50; P = 0.44) overall and 0.49 (95% CI, 0.20-1.17; P = 0.10) in the prespecified subgroup of patients with a baseline PaO2/FiO2 less than 300. CONCLUSIONS: Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12613000505707).

Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial.

BACKGROUND: Equipoise exists regarding the benefits of restricting caloric intake during electrolyte replacement for refeeding syndrome, with half of intensive care specialists choosing to continue normal caloric intake. We aimed to assess whether energy restriction affects the duration of critical illness, and other measures of morbidity, compared with standard care. METHODS: We did a randomised, multicentre, single-blind clinical trial in 13 hospital intensive care units (ICUs) in Australia (11 sites) and New Zealand (two sites). Adult critically ill patients who developed refeeding syndrome within 72 h of commencing nutritional support in the ICU were enrolled and allocated to receive continued standard nutritional support or protocolised caloric restriction. 1:1 computer-based randomisation was done in blocks of variable size, stratified by enrolment serum phosphate concentration (>0·32 mmol/L vs ≤0·32 mmol/L) and body-mass index (BMI; >18 kg/m(2)vs ≤18 kg/m(2)). The primary outcome was the number of days alive after ICU discharge, with 60 day follow-up, in a modified intention-to-treat population of all randomly allocated patients except those mistakenly enrolled. Days alive after ICU discharge was a composite outcome based on ICU length of stay, overall survival time, and mortality. The Refeeding Syndrome Trial was registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR number 12609001043224). FINDINGS: Between Dec 3, 2010, and Aug 13, 2014, we enrolled 339 adult critically ill patients: 170 were randomly allocated to continued standard nutritional support and 169 to protocolised caloric restriction. During the 60 day follow-up, the mean number of days alive after ICU discharge in 165 assessable patients in the standard care group was 39·9 (95% CI 36·4-43·7) compared with 44·8 (95% CI 40·9-49·1) in 166 assessable patients in the caloric restriction group (difference 4·9 days, 95% CI -2·3 to 13·6, p=0·19). Nevertheless, protocolised caloric restriction improved key individual components of the primary outcome: more patients were alive at day 60 (128 [78%] of 163 vs 149 [91%] of 164, p=0·002) and overall survival time was increased (48·9 [SD 1·46] days vs 53·65 [0·97] days, log-rank p=0·002). INTERPRETATION: Protocolised caloric restriction is a suitable therapeutic option for critically ill adults who develop refeeding syndrome. We did not identify any safety concerns associated with the use of protocolised caloric restriction. FUNDING: National Health and Medical Research Council of Australia.

Critical care services and 2009 H1N1 influenza in Australia and New Zealand.

BACKGROUND: Planning for the treatment of infection with the 2009 pandemic influenza A (H1N1) virus through health care systems in developed countries during winter in the Northern Hemisphere is hampered by a lack of information from similar health care systems. METHODS: We conducted an inception-cohort study in all Australian and New Zealand intensive care units (ICUs) during the winter of 2009 in the Southern Hemisphere. We calculated, per million inhabitants, the numbers of ICU admissions, bed-days, and days of mechanical ventilation due to infection with the 2009 H1N1 virus. We collected data on demographic and clinical characteristics of the patients and on treatments and outcomes. RESULTS: From June 1 through August 31, 2009, a total of 722 patients with confirmed infection with the 2009 H1N1 virus (28.7 cases per million inhabitants; 95% confidence interval [CI], 26.5 to 30.8) were admitted to an ICU in Australia or New Zealand. Of the 722 patients, 669 (92.7%) were under 65 years of age and 66 (9.1%) were pregnant women; of the 601 adults for whom data were available, 172 (28.6%) had a body-mass index (the weight in kilograms divided by the square of the height in meters) greater than 35. Patients infected with the 2009 H1N1 virus were in the ICU for a total of 8815 bed-days (350 per million inhabitants). The median duration of treatment in the ICU was 7.0 days (interquartile range, 2.7 to 13.4); 456 of 706 patients (64.6%) with available data underwent mechanical ventilation for a median of 8 days (interquartile range, 4 to 16). The maximum daily occupancy of the ICU was 7.4 beds (95% CI, 6.3 to 8.5) per million inhabitants. As of September 7, 2009, a total of 103 of the 722 patients (14.3%; 95% CI, 11.7 to 16.9) had died, and 114 (15.8%) remained in the hospital. CONCLUSIONS: The 2009 H1N1 virus had a substantial effect on ICUs during the winter in Australia and New Zealand. Our data can assist planning for the treatment of patients during the winter in the Northern Hemisphere.

Ability of pulse contour and esophageal Doppler to estimate rapid changes in stroke volume.

OBJECTIVE: Two technologies to acquire beat-to-beat stroke volume values exist, pulse contour analysis and esophageal Doppler monitoring. Pulse contour analysis assumes fixed aortic impedance. Esophageal Doppler assumes a constant proportional descending aortic flow and diameter. These assumptions may not be correct as arterial tone or myocardial contractility vary. We tested these relationships in the setting of rapidly changing stroke volumes and different cardiovascular states over a period of 10-15 cardiac cycles. DESIGN AND SETTING: In a university research facility we compared beat-to-beat changes in stroke volume as measure by aortic root flow probe or conductance catheter to pulse contour analysis and stroke distance as measured by esophageal Doppler. SUBJECTS: Five purpose-bred research hounds. INTERVENTIONS: To obtain a wide range of rapidly changing stroke volumes measurements were made during transient inferior vena cava occlusion. Data were gathered under baseline conditions and during norepinephrine, nitroprusside, and dobutamine infusions. MEASUREMENTS AND RESULTS: The pulse contour stroke volumes and esophageal Doppler stroke distance paralleled flow probe stroke volumes under all conditions (R(2)=0.89 for all measures). However, the absolute changes and proportional changes and the absolute values for both surrogate measures differed from absolute stroke volumes. Bland-Altman analysis showed no consistent bias or degree of precision across all animals under any given cardiovascular state. CONCLUSIONS: Both pulse contour stroke volumes and esophageal Doppler derived stroke distance estimates yield significant correlations with aortic root flow probe. However, the absolute values, absolute changes, or proportional changes may not reflect actual stroke volumes as cardiovascular state varies, making their use in estimating absolute changes in stroke volume potentially inaccurate.