A Multicenter Trial of Vena Cava Filters in Severely Injured Patients.

BACKGROUND: Whether early placement of an inferior vena cava filter reduces the risk of pulmonary embolism or death in severely injured patients who have a contraindication to prophylactic anticoagulation is not known. METHODS: In this multicenter, randomized, controlled trial, we assigned 240 severely injured patients (Injury Severity Score >15 [scores range from 0 to 75, with higher scores indicating more severe injury]) who had a contraindication to anticoagulant agents to have a vena cava filter placed within the first 72 hours after admission for the injury or to have no filter placed. The primary end point was a composite of symptomatic pulmonary embolism or death from any cause at 90 days after enrollment; a secondary end point was symptomatic pulmonary embolism between day 8 and day 90 in the subgroup of patients who survived at least 7 days and did not receive prophylactic anticoagulation within 7 days after injury. All patients underwent ultrasonography of the legs at 2 weeks; patients also underwent mandatory computed tomographic pulmonary angiography when prespecified criteria were met. RESULTS: The median age of the patients was 39 years, and the median Injury Severity Score was 27. Early placement of a vena cava filter did not result in a significantly lower incidence of symptomatic pulmonary embolism or death than no placement of a filter (13.9% in the vena cava filter group and 14.4% in the control group; hazard ratio, 0.99; 95% confidence interval [CI], 0.51 to 1.94; P = 0.98). Among the 46 patients in the vena cava filter group and the 34 patients in the control group who did not receive prophylactic anticoagulation within 7 days after injury, pulmonary embolism developed in none of those in the vena cava filter group and in 5 (14.7%) in the control group, including 1 patient who died (relative risk of pulmonary embolism, 0; 95% CI, 0.00 to 0.55). An entrapped thrombus was found in the filter in 6 patients. CONCLUSIONS: Early prophylactic placement of a vena cava filter after major trauma did not result in a lower incidence of symptomatic pulmonary embolism or death at 90 days than no placement of a filter. (Funded by the Medical Research Foundation of Royal Perth Hospital and others; Australian New Zealand Clinical Trials Registry number, ACTRN12614000963628.).

Incremental cost of venous thromboembolism in trauma patients with contraindications to prophylactic anticoagulation: a prospective economic study.

Venous thromboembolism (VTE) is common in patients after major trauma. Attributable cost of VTE and whether this is related to the severity of injury have not been thoroughly investigated. We aimed to define the hospitalization costs of VTE and assess whether the costs were related to the severity of injury in this prospective economic study. Cost data of each patient enrolled in the da Vinci trial were drawn from hospital finance departments and standardized to 2020 Australian dollars (A$); and Injury Severity Score and Trauma Embolic Scoring System were used to quantify the severity of injury. Of the 223 patients who had complete financial cost data available until day-90 follow-up, 37 (16.6%) developed VTE, including upper limb (n = 3) and lower limb deep vein thrombosis (n = 25), pulmonary embolism (n = 7) and clots entrapped in a vena cava filter. The median total radiology (A$4307) as well as the hospitalization costs (A$138,526) of those who had VTE were significantly higher than those without VTE (A$1210; p < 0.001 and A$105,842; p = 0.023, respectively). The incremental hospitalization cost attributable to VTE was most apparent among those who had sustained extremely severe injuries, and estimated to be between A$43,292 (95% confidence interval [CI] 12,624-73,961, p = 0.006) and 41,680 (95%CI 7766-75,594, p = 0.016) after adjusted for Trauma Embolic Scoring System and Injury Severity Scores, respectively. VTE was common after major trauma and incurred a substantial incremental financial cost to the healthcare system, especially among those who had extremely severe injuries.

Cost-effectiveness of early placement of vena cava filters to prevent symptomatic pulmonary embolism in patients with contraindications to prophylactic anticoagulant.

INTRODUCTION: Vena cava filters have been used as a primary means to prevent symptomatic pulmonary embolism (PE) in trauma patients who cannot be anticoagulated after severe injury, but the economic implications for this practice remain unclear. METHODS: Using a healthcare system perspective to analyze the a priori primary outcome of the da Vinci trial, we report the cost-effectiveness of using vena cava filters as a primary means to prevent PE in patients who have contraindications to prophylactic anticoagulation after major trauma. RESULTS: Of the 240 patients enrolled, complete, prospectively collected, hospital cost data during the entire hospital stay - including costs for the filter, medical/nursing/allied health staff, medical supplies, pathology tests, and radiological imaging - were available in 223 patients (93%). Patients allocated to the filter group (n = 114) were associated with a reduced risk of PE (0.9%) compared to those in the control group (n = 109, 5.5%; p = 0.048); and the filter's benefit was more pronounced among those who could not be anticoagulated within 7 days (filter: 0% vs control: 16%, Bonferroni-corrected p = 0.02). Overall, the cost needed to prevent one PE was high (AUD $379,760), but among those who could not be anticoagulated within 7 days, the costs to prevent one PE (AUD $36,156; ~ USD $26,032) and gain one quality-adjusted life-year (AUD $30,903; ~ USD $22,250) were substantially lower. CONCLUSION: The cost of using a vena cava filter to prevent PE for those who have contraindications to prophylactic anticoagulation within 3 days of injury is prohibitive, unless such contraindications remain for longer than 7 days. (Australian New Zealand Clinical Trials Registry no.: ACTRN12614000963628).

Anemia in hospitalized patients: an overlooked risk in medical care.

BACKGROUND: This study investigated the association between nadir anemia and mortality and length of stay (LOS) in a general population of hospitalized patients. STUDY DESIGN AND METHODS: A retrospective cohort study of tertiary hospital admissions in Western Australia between July 2010 and June 2015. Outcome measures were in-hospital mortality and LOS. RESULTS: Of 80,765 inpatients, 45,675 (56.55%) had anemia during admission. Mild and moderate/severe anemia were independently associated with increased in-hospital mortality (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.36-1.86, p = 0.001; OR 2.77, 95% CI 2.32-3.30, p < 0.001, respectively). Anemia was also associated with increased LOS, demonstrating a larger effect in emergency (mild anemia-incident rate ratio [IRR] 1.52, 95% CI 1.48-1.56, p < 0.001; moderate/severe anemia-IRR 2.18, 95% CI 2.11-2.26, p < 0.001) compared to elective admissions (mild anemia-IRR 1.30, 95% CI 1.21-1.41, p < 0.001; moderate/severe anemia-IRR 1.69, 95% CI 1.55-1.83, p < 0.001). LOS was longer in patients who developed anemia during admission compared to those who had anemia on admission (IRR 1.13, 95% CI 1.10-1.17, p < 0.001). Red cell transfusion was independently associated with 2.23 times higher odds of in-hospital mortality (95% CI 1.89-2.64, p < 0.001) and 1.31 times longer LOS (95% CI 1.25-1.37, p < 0.001). CONCLUSION: More than one-third of patients not anemic on admission developed anemia during admission. Even mild anemia is independently associated with increased mortality and LOS; however, transfusion to treat anemia is an independent and additive risk factor.

Differential disruption of blood-brain barrier in severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of death and disability in young adults, but not much is known about the incidence and characteristics of blood-brain barrier (BBB) dysfunction in this group. In this proof of concept study, we sought to quantify the incidence of BBB dysfunction (defined as a cerebrospinal fluid (CSF)-plasma albumin quotient of ≥0.007) and examine the relationship between plasma and CSF levels of proteins and electrolytes, in patients with severe TBI. METHODS: We recruited 30 patients, all of whom were receiving hypertonic 20 % saline infusion for intracranial hypertension and had external ventricular drains in situ. Simultaneous CSF and blood samples were obtained. Biochemical testing was performed for sodium, osmolality, potassium, glucose, albumin, immunoglobulin-G, and total protein. RESULTS: Eleven patients (37 %) showed evidence of impairment of passive BBB function, with a CSF-plasma albumin quotient of ≥0.007. There were strong positive correlations seen among CSF-plasma albumin quotient and CSF-plasma immunoglobulin-G quotient and CSF-plasma total protein quotient (r = 0.967, P < 0.001 and r = 0.995, P < 0.001, respectively). We also found a higher maximum intracranial pressure (24 vs. 21 mmHg, P = 0.029) and a trend toward increased mortality (27 vs. 11 %, P = 0.33) in patients with BBB disruption. CONCLUSIONS: In summary, passive BBB dysfunction is common in patients with severe TBI, and may have important implications for effectiveness of osmotherapy and long-term outcomes. Also, our results suggest that the CSF-plasma total protein quotient, a measurement which is readily available, can be used instead of the CSF-plasma albumin quotient for evaluating BBB dysfunction.

Long-term outcomes after using retrievable vena cava filters in major trauma patients with contraindications to prophylactic anticoagulation.

PURPOSE: To investigate the long-term outcomes of using vena cava filters to prevent symptomatic pulmonary embolism (PE) in major trauma patients who have contraindications to prophylactic anticoagulation. METHODS: This was an a priori sub-study of a randomized controlled trial (RCT) involving long-term outcome data of 223 patients who were enrolled in Western Australia. State-wide clinical information system, radiology database and death registry were used to assess long-term outcomes, including incidences of venous thromboembolism, venous injury and mortality beyond day-90 follow-up. RESULTS: The median follow-up time of 198 patients (89%) who survived beyond 90 days was 65 months (interquartile range 59-73). Ten patients (5.1%) died after day-90 follow-up; and four patients developed venous thromboembolism, including two with symptomatic PE, all allocated to the control group (0 vs 4%, p = 0.043). Inferior vena cava injuries were not recorded in any patients. The mean total hospitalization cost, including the costs of the filter and its insertion and removal, to prevent one short- or long-term symptomatic PE was A$284,820 (€193,678) when all enrolled patients were considered. The number of patients needed to treat (NNT = 5) and total hospitalization cost to prevent one symptomatic PE (A$1,205 or €820) were, however, substantially lower when the filter was used only for patients who could not be anticoagulated within seven days of injury. CONCLUSION: Long-term complications related to retrievable filters were rare, and the cost of using filters to prevent symptomatic PE was acceptable when restricted to those who could not be anticoagulated within seven days of severe injury.

A prospective ex vivo biomechanical analysis of retrievable inferior vena cava filters.

OBJECTIVE: In the present study, we investigated the structural integrity of inferior vena cava (IVC) filters after their retrieval. METHODS: A prospective ex vivo biomechanical analysis was performed of the structural integrity of 100 IVC filters used in a randomized controlled trial to evaluate the effectiveness of prophylactic IVC filters in preventing mortality or symptomatic pulmonary embolism in major trauma patients. RESULTS: Of the 100 included patients, 7 (7%) had required more than one attempt to remove the filter. The median duration of the filter left in situ was 54 days (interquartile range, 17-101 days). During the initial attempt to remove six filters (6%), thrombi were found entrapped and required 4 weeks of systemic anticoagulation therapy before the filters could be removed in a second attempt. A positive correlation was found between the duration of the filter left in situ and the loss in metallic elasticity of the nitinol alloy of the filter struts (Pearson correlation coefficient, 0.232; P = .008). One filter was adherent to the IVC wall and required open surgical removal 227 days after its initial placement. One of the six long struts of the filter had been fractured during the removal process, with evidence of hardening to bending stress in the remaining five struts of the fractured filter compared with the struts of the 25 intact filters. Fibrous endothelial tissue (73%) and thrombi (33%) adherent to the retrieved filters were frequently observed. The presence of adherent fibrous tissue was not significantly related statistically to the duration of the filter left in situ (P = .353) but was more common among the patients who had had a delay in receiving prophylactic anticoagulation therapy (mean difference, 2 days; 95% confidence interval, 0.6-3.3; P = .039). CONCLUSIONS: Metallic fatigue might account for IVC filter strut fractures. Fibrous endothelial tissue adherent to the filters was common, especially for those with a delay in receiving prophylactic anticoagulation therapy.

A comparison of central and mixed venous oxygen saturation in circulatory failure.

OBJECTIVE: The purpose of this study was to evaluate whether central venous oxygen saturation can be used as an alternative to mixed venous oxygen saturation in patients with cardiogenic and septic shock. DESIGN: Prospective clinical study. SETTING: A tertiary intensive care unit in a university hospital. PARTICIPANTS: Twenty patients with cardiogenic or septic shock requiring a pulmonary artery catheter and inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The central venous oxygen saturation overestimated the mixed venous oxygen saturation by a mean bias (or an absolute difference) of 6.9%, and the 95% limits of agreement were large (-5.0% to 18.8%). The difference between central and mixed venous oxygen saturation appeared to be more significant when mixed venous oxygen saturation was <70%. The changes in central and mixed venous oxygen saturation did not follow the line of perfect agreement closely in different clinical conditions. The central or mixed venous oxygen saturation had a significant ability to predict the status of cardiac output state, but this ability was reduced when the effect of hyperoxia was not considered. CONCLUSION: Central and mixed venous oxygen saturation measurements are not interchangeable numerically.

The impact of arterial oxygen tension on venous oxygen saturation in circulatory failure.

Central and mixed venous oxygen saturations have been used to guide resuscitation in circulatory failure, but the impact of arterial oxygen tension on venous oxygen saturation has not been thoroughly evaluated. This observational study investigated the impact of arterial oxygen tension on venous oxygen saturation in circulatory failure. Twenty critically ill patients with circulatory failure requiring mechanical ventilation and a pulmonary artery catheter in an intensive care unit in a tertiary hospital in Western Australia were recruited. Samples of arterial blood, central venous blood, and mixed venous blood were simultaneously and slowly drawn from the arterial, central venous, and pulmonary artery catheter, respectively, at baseline and after the patient was ventilated with 100% inspired oxygen for 5 min. The blood samples were redrawn after a significant change in cardiac index (>or =10%) from the baseline, occurring within 24 h of study enrollment while the patient was ventilated with the same baseline inspired oxygen concentration, was detected. An increase in inspired oxygen concentration significantly increased the arterial oxygen tension from 12.5 to 38.4 kPa (93.8-288 mmHg) (mean difference, 25.9 kPa; 95% confidence interval [CI], 7.5-31.9 kPa; P < 0.001) and the venous oxygen saturation from 69.9% to 76.5% (mean difference, 6.6%; 95% CI, 5.3% - 7.9%; P < 0.001). The effect of arterial oxygen tension on venous oxygen saturation was more significant than the effect associated with changes in cardiac index (mean difference, 2.8%; 95% CI, -0.2% to 5.8%; P = 0.063). In conclusion, arterial oxygen tension has a significant effect on venous oxygen saturation, and this effect is more significant and consistent than the effect associated with changes in cardiac index.

The effect of prognostic data presentation format on perceived risk among surrogate decision makers of critically ill patients: a randomized comparative trial.

PURPOSE: The purpose of this study is to determine whether varying the format used to present prognostic data alters the perception of risk among surrogate decision makers in the intensive care unit (ICU). METHODS: This was a prospective randomized comparative trial conducted in a 23-bed adult tertiary ICU. Enrolled surrogate decision makers were randomized to 1 of 2 questionnaires, which presented hypothetical ICU scenarios, identical other than the format in which prognostic data were presented (eg, frequencies vs percentages). Participants were asked to rate the risk associated with each prognostic statement. RESULTS: We enrolled 141 surrogate decision makers. The perception of risk varied significantly dependent on the presentation format. For "quantitative data," risks were consistently perceived as higher, when presented as frequencies (eg, 1 in 50) compared with equivalent percentages (eg, 2%). Framing "qualitative data" in terms of chance of "death" rather than "survival" led to a statistically significant increase in perceived risks. Framing "quantitative" data in this way did not significantly affect risk perception. CONCLUSION: Data format had a significant effect on how surrogate decision makers interpreted risk. Qualitative statements are interpreted widely and affected by framing. Where possible, multiple quantitative formats should be used for presenting prognostic information.

Early experience with influenza A H1N109 in an Australian intensive care unit.

Influenza is a common seasonal viral infection that affects large numbers of people. In early 2009, many people were admitted to hospitals in Mexico with severe respiratory failure following an influenza-like illness, subtyped as H1N1. An increased mortality rate was observed. By June 2009, H1N1 was upgraded to pandemic status. In June-July, Australian ICUs were experiencing increased activity due to the influenza pandemic. While hospitals implemented plans for the pandemic, the particularly heavy demand to provide critical care facilities to accommodate an influx of people with severe respiratory failure became evident and placed a great burden on provision of these services. This paper describes the initial experience (June to mid September) of the pandemic from the nursing perspective in a single Australian ICU. Patients were noted to be younger with a higher proportion of women, two of whom were pregnant. Two patients had APACHE III comorbidity. Of the 31 patients admitted during this period, three patients died in ICU and one patient died in hospital. Aerosol precautions were initiated for all patients. The requirement for single room accommodation placed enormous demands for bed management in ICU. Specific infection control procedures were developed to deal with this new pandemic influenza.

C-reactive protein concentration as a predictor of in-hospital mortality after ICU discharge: a nested case-control study.

PURPOSE: To assess the ability of potential clinical predictors and inflammatory markers to predict in-hospital mortality after patient discharge from the intensive care unit. SETTING AND PARTICIPANTS: 1272 patients who survived their index admission to a 22-bed multidisciplinary ICU of a university hospital in 2004. DESIGN: Nested case-control study with two concurrent control patients for each case of post-ICU discharge in hospital mortality. RESULTS: There were 29 unexpected in-hospital deaths after ICU discharge (2.3%). C-reactive protein (CRP) concentrations within 24 hours of ICU discharge were available for 14 of these 29 patients and 22 concurrent control patients. CRP concentration at ICU discharge was associated with subsequent mortality (mean CRP concentrations: cases, 204 mg/L v controls, 63 mg/L; P = 0.001). CRP concentration remained significantly associated with post-ICU mortality after adjustment with other potential predictors of mortality (odds ratio [OR] of death for a 10mg/L increase in CRP concentration, 1.27; 95% CI, 1.09-1.49; P = 0.005) and with propensity score (OR, 1.19; 95% CI, 1.05-1.33; P=0.004). The area under the receiver operating characteristic curve for CRP concentrations to predict in-hospital mortality was 0.87 (95% CI, 0.73-0.99; P=0.001). The destination and timing of ICU discharge, SOFA (Sequential Organ Failure Assessment) score, white cell count and fibrinogen concentration at ICU discharge were not significantly associated with in-hospital mortality after ICU discharge. CONCLUSIONS: A high CRP concentration at ICU discharge is an independent predictor of subsequent in-hospital mortality. Prospective cohort studies in ICUs with different casemix, discharge criteria and post-ICU mortality rates are needed to validate and generalise our findings.