Twenty percent human albumin solution fluid bolus administration therapy in patients after cardiac surgery-II: a multicentre randomised controlled trial.

PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.

Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-ll (HAS FLAIR-II) trial.

Background: Fluid bolus therapy with 20% albumin may shorten the duration of vasopressor therapy in patients after cardiac surgery. Objective: To describe the study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial. Design, setting, participants and intervention: HAS FLAIR-II is a phase 2b, multicentre, parallel group, openlabel, randomised controlled trial that will be conducted at six Australian intensive care units. Patients requiring fluid bolus therapy after cardiac surgery will be randomly assigned in a 1:1 ratio to the intervention of fluid bolus therapy with 20% albumin or a comparator of fluid bolus therapy with a crystalloid solution. Main outcome measures: The primary outcome measure is the cumulative duration of vasopressor therapy. Secondary outcomes include vasopressor use, service utilisation, and mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusion: The study protocol and statistical analysis plan will guide the conduct and analysis of the HAS FLAIR-II trial, such that analytical and reporting biases are minimised. Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN No. 12620000137998).

20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients After Cardiac Surgery (the HAS FLAIR Study).

OBJECTIVE: To compare the effects of fluid bolus therapy using 20% albumin versus crystalloid on fluid balance, hemodynamic parameters, and intensive care unit (ICU) treatment effects in post-cardiac surgery patients. DESIGN: Sequential period open-label pilot study. SETTING: University teaching hospital. PARTICIPANTS: One hundred adult cardiac surgery patients who were prescribed fluid bolus therapy to correct hypotension or perceived hypovolemia or to optimize cardiac index during the first 24 hours in the ICU. INTERVENTIONS: The first 50 patients were treated with crystalloid fluid bolus therapy in the first period (control), and 50 patients with up to 2 treatments of 100 mL of 20% albumin fluid bolus therapy in the second period (intervention), followed by crystalloid therapy if needed. MEASUREMENTS AND MAIN RESULTS: Demographic characteristics were similar at baseline. The intervention was associated with a less positive median fluid balance in the first 24 hours (albumin: 1,100 [650-1,960] v crystalloid: 1,970 [1,430-2,550] p = 0.001), fewer episodes of fluid bolus therapy (3 [2-5] v 5 [4-7]; p < 0.0001) and a lesser volume of fluid bolus therapy (700 [200-1,450] v 1,500 mL/24 h [1,100-2,250]; p < 0.0001). The intervention also was associated with a decreased median overall dose of norepinephrine in the first 24 hours of ICU stay (19 [0-52] v 47 µg/kg/24 hours [0-134]; p = 0.025) and shorter median time to cessation of norepinephrine (17 [5-28] v 28 hours [20-48]; p = 0.002). CONCLUSION: Post-cardiac surgery fluid bolus therapy with 20% albumin when compared with crystalloid fluid resulted in less positive fluid balance as well as several hemodynamic and potential ICU treatment advantages.

Intensive care implications of epidemic thunderstorm asthma.

OBJECTIVE: To investigate the environmental precipitants, treatment and outcome of critically ill patients affected by the largest and most lethal reported epidemic of thunderstorm asthma. DESIGN, SETTING AND PARTICIPANTS: Retrospective multicentre observational study. Meteorological, airborne particulate and pollen data, and a case series of 35 patients admitted to 15 intensive care units (ICUs) due to the thunderstorm asthma event of 21-22 November 2016, in Victoria, Australia, were analysed and compared with 1062 total ICU-admitted Australian patients with asthma in 2016. MAIN OUTCOME MEASURES: Characteristics and outcomes of total ICU versus patients with thunderstorm asthma, the association between airborne particulate counts and storm arrival, and ICU resource utilisation. RESULTS: All 35 patients had an asthma diagnosis; 13 (37%) had a cardiac or respiratory arrest, five (14%) died. Compared with total Australian ICU-admitted patients with asthma in 2016, patients with thunderstorm asthma had a higher mortality (15% v 1.3%, P < 0.001), were more likely to be male (63% v 34%, P < 0.001), to be mechanically ventilated, and had shorter ICU length of stay in survivors (median, 31.8 hours [interquartile range (IQR), 14.8-43.6 hours] v 40.7 hours [IQR, 22.3-75.1 hours]; P = 0.025). Patients with cardiac arrest were more likely to be born in Asian or subcontinental countries (5/10 [50%] v 4/25 [16%]; relative risk, 3.13; 95% CI, 1.05-9.31). A temporal link was demonstrated between airborne particulate counts and arrival of the storm. The event used 15% of the public ICU beds in the region. CONCLUSION: Arrival of a triggering storm is associated with an increase in respirable airborne particles. Affected critically ill patients are young, have a high mortality, a short duration of bronchospasm, and a prior diagnosis of asthma is common.

Intensity of early correction of hyperglycaemia and outcome of critically ill patients with diabetic ketoacidosis.

OBJECTIVES: To determine the impact of the intensity of early correction of hyperglycaemia on outcomes in patients with diabetic ketoacidosis (DKA) admitted to the intensive care unit. METHODS: We studied adult patients with DKA admitted to 171 ICUs in Australia and New Zealand from 2000 to 2013. We used their blood glucose levels (BGLs) in the first 24 hours after ICU admission to determine whether intensive early correction of hyperglycemia to ≤ 180 mg/dL was independently associated with hypoglycaemia, hypokalaemia, hypo-osmolarity or mortality, compared with partial early correction to > 180 mg/dL as recommended by DKA-specific guidelines. RESULTS: Among 8553 patients, intensive early correction of BGL was applied to 605 patients (7.1%). A greater proportion of these patients experienced hypoglycaemia (20.2% v 9.1%; P < 0.001) and/or hypo-osmolarity (29.4% v 22.0%; P < 0.001), but not hypokalaemia (16.7% v 15.6%; P = 0.47). Overall, 11 patients (1.8%) in the intensive correction group and 112 patients (1.4%) in the partial correction group died (P = 0.42). However, after adjustment for illness severity, partial early correction of BGL was independently associated with a lower risk of hypoglycaemia (odds ratio [OR], 0.38; 95% CI, 0.30-0.48; P < 0.001), lower risk of hypo-osmolarity (OR, 0.80; 95% CI, 0.65-0.98; P < 0.03) and lower risk of death (OR, 0.44; 95% CI, 0.22-0.86; P = 0.02). CONCLUSIONS: In a large cohort of patients with DKA, partial early correction of BGL according to DKA-specific guidelines, when compared with intensive early correction of BGL, was independently associated with a lower risk of hypoglycaemia, hypo-osmolarity and death.

Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus.

Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pretreatment with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain.