Recent Research

Prophylactic anticoagulation in the critically ill, ICU telemedicine outcomes, and more.


Age-adjusted D-dimer cutoff appears better at ruling out PE

D-dimer cutoffs adjusted for age performed better than a fixed D-dimer cutoff for safely ruling out pulmonary embolism (PE), especially in elderly patients, according to a recent study.

Researchers performed a multicenter prospective management outcome study in 19 centers in Europe from Jan. 1, 2010, to Feb. 28, 2010. The study's objective was to prospectively validate whether an age-adjusted D-dimer cutoff (age x 10 in patients ≥50 years of age) had better diagnostic yield than the conventional D-dimer cutoff in patients in whom PE was suspected. The study involved consecutive outpatients who presented to EDs with clinically suspected PE, defined as acute-onset or worsening shortness of breath or chest pain without another obvious cause.

Patients were evaluated by a sequential diagnostic strategy that was based on clinical probability according to the simplified revised Geneva score or the 2-level Wells score; highly sensitive D-dimer measurement; and CT pulmonary angiography (CTPA). Patients whose D-dimer value fell between the usual cutoff (500 μg/L) and their age-adjusted cutoff didn't receive CPTA or treatment but were formally followed for 3 months. The study's primary outcome was the diagnostic strategy's failure rate, as defined by thromboembolic events during the 3 months of follow-up in patients who didn't receive anticoagulants because of a negative age-adjusted D-dimer result. Three independent experts who were blinded to the criteria for ruling out PE at study inclusion adjudicated all suspected venous thromboembolic events and deaths. The study results appeared in the March 19 Journal of the American Medical Association.

Overall, 3,346 patients with suspected PE were initially included in the study. Of these, 22 did not have a D-dimer test performed and 1 withdrew consent. The prevalence of PE was 19%. A total of 2,898 patients had a nonhigh or unlikely clinical probability of PE, and of these, 817 (28.2%) had a D-dimer level below 500 μg/L and 337 had a D-dimer level that fell between the conventional cutoff and their age-adjusted cutoff. Patients with a D-dimer level higher than 500 μg/dL but lower than their age-adjusted cutoff had a 3-month diagnostic failure rate of 0.3% (95% CI, 0.1% to 1.7%).

Seven hundred seventy-six patients were at least 75 years old, and of these, 673 had a nonhigh clinical probability of PE. In this group of older patients, the age-adjusted cutoff versus the 500 µg/L cutoff allowed more patients to have PE excluded based on D-dimer testing (200 of 673 vs. 43 of 673, or 29.7% vs. 6.4%). No additional false-negative findings were noted with use of the age-adjusted cutoff in this group.

The authors noted that their study was not randomized and that the different institutions involved used different tools to assess pretest probability, as well as different commercial D-dimer assays, among other limitations. However, they concluded that age-adjusted D-dimer cutoffs, when combined with probability assessment, ruled out PE in more ED patients than the conventional cutoff and were associated with a low risk for subsequent symptomatic venous thromboembolism, especially in patients at least 75 years of age.

“Future studies should assess the clinical usefulness of the age-adjusted D-dimer cutoff in clinical practice,” the authors wrote. “Whether the age-adjusted cutoff can result in improved cost-effectiveness or quality of care remains to be demonstrated.”

Prophylactic anticoagulation associated with better all-cause mortality vs. mechanical devices for VTE prevention in critically ill

Critically ill patients should receive prophylactic anticoagulation over mechanical device prophylaxis for preventing venous thromboembolism (VTE), a study found.

In an observational study, researchers examined data from adult patients in 271 ICUs in 31 U.S. states, who were discharged alive or dead from Jan. 1, 2008, to Sept. 30, 2010. Patients were assigned to prophylactic anticoagulation, mechanical devices, both, or neither, based on clinical judgment. The main outcomes were all-cause ICU and in-hospital mortality after adjustment for acuity, propensity to receive VTE prophylaxis, and management with mechanical ventilation. Researchers compared outcomes for those on prophylactic anticoagulation versus mechanical devices in a separate paired propensity-matched cohort. Results were published in the July Chest.

Roughly one-third of patients were prescribed anticoagulation without a device, one-third got a device only, and one-third received both. After adjustment, the patients treated with prophylactic anticoagulation were the only group with significantly lower mortality risk than those who didn't receive VTE prophylaxis (ICU mortality hazard ratio [HR], 0.81; hospital mortality, HR, 0.84; P<0.0001 for both). Patients receiving mechanical prophylaxis didn't have a lower mortality risk than those without VTE prophylaxis. Also, in paired propensity matching, those who were given prophylactic anticoagulation had lower mortality than those who received mechanical device prophylaxis (ICU sub-HR, 0.82; hospital sub-HR, 0.82; P<0.001 for both).

Previous trials with non-critically ill patients finding that prophylactic anticoagulation and mechanical devices were equally effective do not appear to apply to the critically ill adult population, the authors noted. In addition, comparing results of the prophylactic anticoagulation group to the combined prophylactic group suggests that mechanical devices may actually counteract some of the benefits of prophylactic anticoagulation, they added. “The odds of dying in the hospital for the mechanical device only group were significantly higher than that of the group not managed with VTE prophylaxis, raising concern that these devices could be harmful under some circumstances,” they wrote. In sum, this study supports current American College of Chest Physicians guidelines advising the preferential use of anticoagulants for VTE prevention for adult critically ill patients without contraindications.

Depletive fluid management strategy may lower risk of ventilator-associated complications, pneumonia

Using a depletive fluid management strategy when starting the weaning process from mechanical ventilation may lower the risk of ventilator-associated pneumonia (VAP), a study found.

Researchers used data from the B-type natriuretic peptide for the fluid Management of Weaning (BMW) randomized controlled trial, performed in 9 intensive care units across Europe and South America from May 2007 to July 2009, to compare the cumulative incidence of ventilator-associated complications (VAC) and VAP. A computer-driven automated weaning system was used in all ventilated patients to standardize the weaning process.

Inclusion criteria were those allowing early initiation of ventilator weaning:

  • endotracheal mechanical ventilation for at least 24 hours,
  • SpO2 ≥90% with FiO2 ≤50% and PEEP ≤8 cm H2O,
  • hemodynamic stability during the past 12 hours,
  • sedation stopped or decreased over the past 48 hours,
  • stable neurological status with Ramsay score ≤5, and
  • a body temperature >36.0°C and <39.0°C.

Patients were randomized to a biomarker-driven (B-type natriuretic peptide [BNP]) depletive fluid management group or to a usual care group for 14 days. All patients were weaned using a computerized automated system. In the interventional group, on days with a BNP level ≥200 pg/mL, fluid intake was restricted (baseline infusion ≤500 mL/24 hours, parenteral nutrition ≤1,000 mL/24 hours, no saline solutions apart from nutrition and drugs) and furosemide was administered as intravenous bolus doses of 10 to 30 mg every 3 hours, to achieve a target urine output of 4.5 to 9 mL/kg every 3 hours. Extubation was performed as soon as the weaning system dictated, including during the night.

Results were published in the July Chest.

Among 304 patients analyzed, 41 experienced VAP, including 27 (17.8%) in the usual care group vs. 14 (9.2%) in the intervention group (P=0.03). The probabilities of VAC and VAP were both significantly reduced with the interventional strategy with adjustment for weaning outcome. The sub-hazard ratio was 0.44 for VAC (95% CI, 0.22 to 0.87; P=0.02) and 0.50 for VAP (95% CI, 0.25 to 0.96; P=0.03).

Compared to the control group, the interventional strategy was associated with a higher proportion of patients receiving diuretics (124 [81.6%] vs. 108 [71.1%]; P=0.03). The diuretics were used in higher doses (average daily furosemide dose of 40 mg per day vs. 14 mg per day; P<0.0001). This resulted in a significantly more negative fluid balance (average daily fluid balance during weaning of -640 mL per day vs. -37 mL per day; P<0.0001). Patients in the intervention group had a shorter duration of mechanical ventilation (time to successful extubation of 42.4 hours vs. 58.6 hours; P=0.03).

Researchers noted 2 reasons why a depletive fluid management strategy might offer advantages for reducing VAP: An edematous lung may be more susceptible to bacterial infection, and pulmonary edema may exert a direct effect on bacterial colonization and infectivity.

“There is currently no practical guide to fluid management incorporated into guidelines for VAP prevention,” the authors noted. “Whether incorporating a depletive fluid management strategy into a bundle of preventive measures may favorably alter patients' outcomes needs further research.”

Hospitalist clinical decision unit associated with decreased length of stay

A hospitalist-run clinical decision unit (CDU) was associated with decreased length of stay and didn't appear to increase hospital or ED revisit rates, according to a recent study.

Researchers conducted a retrospective cohort study using pre- and post-implementation analysis at a 600-bed urban academic medical center in New Jersey to examine whether a hospitalist-run CDU affected length of stay in observation patients. The 20-bed geographic CDU was run by hospitalists and was located next to the ED. The researchers also analyzed whether the unit affected 30-day revisits to the ED or the hospital. Included patients were observation patients who were discharged from medical-surgical units before and after the CDU was opened, as well as patients who were discharged from the CDU after it opened. The results of the study were published in the June Journal of Hospital Medicine.

A total of 3,735 patients were included in the study, 1,650 who were cared for before the CDU opened, 1,469 who received care in the CDU, and 616 who received care in medical-surgical units after the CDU opened. Researchers examined 2 time periods—July 2010 to January 2011, before the CDU opened, and July 2011 through January 2012, after it opened—and calculated a median length of stay for observation patients in each 7-month period before and after implementation of the CDU. They also determined 30-day revisits to the ED or hospital that necessitated another stay as an observation patient or an inpatient. Patients assigned to the CDU had a shorter median stay than those assigned to medical-surgical observation in the same period (17.6 hours vs. 26.1 hours; P<0.001). The median length of stay in the CDU was also shorter than that for medical-surgical observation 1 year before the CDU was established (17.6 hours vs. 27.1 hours; P<0.001). Revisit rates to the ED or the hospital in the 30 days after discharge were similar regardless of where patients received care.

The authors acknowledged that their study involved only a single academic medical center which had a concomitant initiative to decrease length of stay, among other limitations. However, they concluded that a hospitalist-run geographic CDU was associated with shorter observation stays and did not negatively affect revisit rates. “Implementation of CDUs may be useful for health systems seeking to improve hospital throughput and improve utilization among common but low-acuity patient groups,” the authors wrote. They added that CDUs might need some enhancements to improve transitions of care and that future studies should examine patient and physician satisfaction, as well as costs.

Missed enoxaparin doses for DVT prophylaxis are common, increase risk

It's common for surgery and trauma patients to miss doses of enoxaparin sodium for deep venous thrombosis (DVT) prophylaxis, which in turn increases their risk of DVT, a recent study found.

In a prospective study from February 2007 through September 2012, researchers examined 202 trauma and general surgery patients at a level I trauma center who were prescribed prophylactic enoxaparin. All dosing regimens were included (once daily, twice daily, and dosing adjusted for obesity and renal impairment). Trauma-ward patients received weekly bilateral whole-leg duplex ultrasonography for DVT surveillance, while surgery patients received the testing when DVT was suspected. Results were published in the April JAMA Surgery.

Fifty-nine percent of patients missed at least 1 dose of enoxaparin, and the overall DVT incidence was 15.8%. DVTs occurred in 23.5% of patients who missed at least 1 dose compared to 4.8% of patients who didn't (P<0.01). On univariate analysis, need for mechanical ventilation was associated with DVT (71.8% vs. 44.1%; P<0.05), as was having more than 1 operation (59.3% vs. 40%; P<0.05) and being male (75% vs. 56%; P<0.05). On bivariate logistic regression, independent risk factors for DVT were interrupted enoxaparin therapy (odds ratio [OR], 5.34; P<0.006) and being older than 50 years (OR, 3.12; P<0.03). DVT rates didn't differ between general surgery and trauma patients or by dosing regimens.

The most commonly documented reasons for withholding doses were pending invasive procedures, absence of the patient from the room, and epidural catheter use, but a “surprising” number of doses were withheld without a cause specified, the authors noted. Since the study's conclusion, the hospital has made enoxaparin a quality improvement measure and has educated surgeons about adverse results of missing doses, which has lowered the percentage of doses withheld, they added. “Through nursing and patient education, doses missed because of nursing errors or patient refusal should be eradicated. Missed doses are the only identified risk factor for DVT that can be ameliorated by physicians, and efforts to (do so) should be optimized,” the authors concluded.

ICU telemedicine improved mortality and length of stay

Implementing telemedicine care in the ICU improved mortality and length of stay, according to a large recent study.

The pre/post study measured the effects of implementing telemedicine in 56 ICUs at 32 hospitals from 19 U.S. health care systems. Outcomes from more than 100,000 adult patients treated between 2003 and 2008 were included. Having telemedicine was associated with a significant reduction in mortality, both while in the ICU (hazard ratio [HR], 0.74; P<0.001) and in the hospital generally (HR, 0.84; P<0.001).

Hospital and ICU lengths of stay (LOS) were significantly reduced for patients admitted for a week, 2 weeks, or a month. These reductions were significant in both crude numbers and when adjusted for a number of factors.

The improvement in mortality is notable because prior similar studies did not have adequate power to prove such an association. The finding of improvements in both mortality and LOS suggests that the ICUs were able to more quickly stabilize patients and facilitate their recovery to discharge, ready them for the transition to rehabilitative care, or efficiently transition them to comfort care, the authors said. The study was published in the March Chest.

The researchers also identified especially effective components of telemedicine interventions from the data. Both mortality and LOS were improved by intensivist case review within an hour of admission, timely use of performance data, and adherence to ICU best practices. LOS was also reduced by shorter response time to alerts and alarms. Mortality was improved by interdisciplinary rounds and ICU committee effectiveness. The researchers noted, however, that the individual impact of these components was small, indicating that they had an additive effect.

The authors also drew attention to the finding that physician staffing models were not predictive of outcomes, concluding “it is not the on-site presence of an intensivist that drives better outcomes; rather it is when and how that individual is engaged in case management.” Although the participating hospitals were self-selecting based on their willingness to participate, they were diverse, so the findings should be broadly applicable to a wide variety of hospitals, the study authors said.