Neil Orford

Age of red blood cells and mortality in the critically ill

IntroductionIn critically ill patients, it is uncertain whether exposure to older red blood cells (RBCs) may contribute to mortality. We therefore aimed to evaluate the association between the age of RBCs and outcome in a large unselected cohort of critically ill patients in Australia and New Zealand. We hypothesized that exposure to even a single unit of older RBCs may be associated with an increased risk of death.MethodsWe conducted a prospective, multicenter observational study in 47 ICUs during a 5-week period between August 2008 and September 2008. We included 757 critically ill adult patients receiving at least one unit of RBCs. To test our hypothesis we compared hospital mortality according to quartiles of exposure to maximum age of RBCs without and with adjustment for possible confounding factors.ResultsCompared with other quartiles (mean maximum red cell age 22.7 days; mortality 121/568 (21.3%)), patients treated with exposure to the lowest quartile of oldest RBCs (mean maximum red cell age 7.7 days; hospital mortality 25/189 (13.2%)) had an unadjusted absolute risk reduction in hospital mortality of 8.1% (95% confidence interval = 2.2 to 14.0%). After adjustment for Acute Physiology and Chronic Health Evaluation III score, other blood component transfusions, number of RBC transfusions, pretransfusion hemoglobin concentration, and cardiac surgery, the odds ratio for hospital mortality for patients exposed to the older three quartiles compared with the lowest quartile was 2.01 (95% confidence interval = 1.07 to 3.77).ConclusionsIn critically ill patients, in Australia and New Zealand, exposure to older RBCs is independently associated with an increased risk of death.

Stress Hyperlactatemia Modifies the Relationship Between Stress Hyperglycemia and Outcome: A Retrospective Observational Study*

Objective:To study the effect of stress hyperlactatemia on the association between stress hyperglycemia and mortality. Design:Retrospective cross-sectional observation study. Setting:Three ICUs using arterial blood gases with simultaneous glucose and lactate measurements during ICU stay. Patients:Cohort of 7,925 consecutive critically ill patients. Interventions:None. Measurements and Main Results:We analyzed 152,349 simultaneous measurements of glucose and lactate. We performed multivariable analysis to study the association of different metrics of glucose and lactate with hospital mortality. On day 1, first (p = 0.013), highest (p = 0.001), mean (p = 0.019), and time-weighted mean (p = 0.010) glucose levels were associated with increased mortality. A similar, but stronger, association was seen for corresponding lactate metrics (p < 0.0001 for all). However, once glucose and lactate metrics were entered into the multivariable logistic regression model simultaneously, all measures of glycemia ceased to be significantly associated with hospital mortality regardless of the metrics being used (first, highest, mean, time-weighed; p > 0.05 for all), whereas all lactate metrics remained associated with mortality (p < 0.0001 for all). In patients with at least one episode of moderate hypoglycemia (glucose ⩽ 3.9 mmol/L), glucose metrics were not associated with mortality when studied separately (p > 0.05 for all), whereas lactate was (p < 0.05 for all), but when incorporated into a model simultaneously, highest glucose on day 1 was associated with mortality (p< 0.05), but not other glucose metrics (p > 0.05), whereas all lactate metrics remained associated with mortality (p < 0.05 for all). Conclusions:Stress hyperlactatemia modifies the relationship between hyperglycemia and mortality. There is no independent association between hyperglycemia and mortality once lactate levels are considered.

Skeletal morbidity among survivors of critical illness.

Objectives: To describe the incident fracture rate in survivors of critical illness and to compare fracture risk with population-matched control subjects. Design: Retrospective longitudinal case–cohort study. Setting: A tertiary adult intensive care unit in Australia. Patients: All patients ventilated admitted to intensive care and requiring mechanical ventilation for ≥48 hrs between January 1998 and December 2005. Interventions: None. Measurements and Main Results: New fractures were identified in the study population for the postintensive care unit period (intensive care unit discharge to January 2008). The incident fracture rate and age-adjusted fracture risk of the female intensive care unit population were compared with the general population adult females derived from the Geelong Osteoporosis Study. Over the 8-yr period, a total of 739 patients (258 women, 481 men) were identified. After a median follow-up of 3.7 yrs (interquartile range, 2.0–5.9 yrs) for women and 4.0 yrs (interquartile range, 2.1–6.1 yrs) for men, incident fracture rates (95% confidence interval) per 100 patient years were 3.84 (2.58–5.09) for females 2.41 (1.73–3.09) for males. Compared with an age-matched random population-based sample of women, elderly women were at increased risk for sustaining an osteoporosis-related fracture after critical illness (hazard ratio, 1.65; 95% confidence interval, 1.08–2.52; p = .02). Conclusions: The increase in fracture risk observed in postintensive care unit older females suggests an association between critical illness and subsequent skeletal morbidity. The explanation for this association is not explored in this study and includes the effects of pre-existing patient factors and/or direct effects of critical illness. Prospective research evaluating risk factors, the relationship between critical illness and bone turnover, the extent and duration of bone loss, and the associated morbidity in this population is warranted.

Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients

IMPORTANCE Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. OBJECTIVE To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. MAIN OUTCOMES AND MEASURES Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. RESULTS Hospital costs per patient were

Early diagnosis and treatment of necrotizing fasciitis can improve survival: an observational intensive care unit cohort study

39,508 (interquartile range [IQR],

Effectiveness of a care bundle to reduce central line-associated bloodstream infections.

24,676 to

Changes in Bone Mineral Density in the Year after Critical Illness.

71,431) for 1862 patients who received LMWH compared with

The association between critical illness and changes in bone turnover in adults: a systematic review

40,805 (IQR,

Glycaemic control in Australia and New Zealand before and after the NICE-SUGAR trial: a translational study

24,393 to

A prospective observational study of prevalence and outcomes of patients with Gold Standard Framework criteria in a tertiary regional Australian Hospital.

76,139) for 1862 patients who received UFH (incremental cost, -