Recent Research

Shorter stay and mortality after hip fracture, outcomes from hypothermia, apixaban for acute VTE, and more.


Shorter stay associated with lower mortality after hip fracture

Having a shorter hospital stay after hip fracture was associated with a reduced risk of death within 30 days of discharge, a recent study of patients in New York State found.

The retrospective cohort study used the New York Statewide Planning and Research Cooperative to analyze 188,208 patients admitted for hip fracture from 2000 to 2011. All patients were age 50 years or older, and those who received surgical and nonsurgical treatment were included. Results were published by BMJ on Dec. 10, 2015.

Hospital stays of 11 to 14 days were associated with significantly higher 30-day mortality than 1- to 5-day stays (odds ratio [OR], 1.32; 95% CI, 1.19 to 1.47), the study found. Staying even longer (>14 days) was associated with an even greater increase in mortality risk (OR, 2.03; 95% CI, 1.84 to 2.24). Other factors associated with 30-day mortality were discharge to hospice, older age, metastatic disease, and nonsurgical management. Mortality 30 days after discharge was 4.5% among surgical patients and 10.7% among nonsurgical patients.

These results differ from those of a recent Swedish study, which found lower mortality associated with longer length of stay. The authors noted that in Sweden, almost all hip fracture patients are managed surgically, and the standard of care is to stabilize fractures within 24 hours. Still, the New York patients had lower inpatient and postdischarge mortality than the Swedish patients, they pointed out. Another difference is that a recent study showed that a much higher percentage of Swedish patients are discharged home after hospitalization (31.1% in that study vs. 12.9% in the current New York study). Length of stay is also much longer in Sweden. It's not clear exactly how these various differences impacted outcomes, the authors noted.

The results of this study lead to the conclusion that longer length of stay is probably a marker of greater comorbidities or complications, at least in New York, said the authors, who noted their findings might not be generalizable even to other states. The study “suggests prolonging admission to hospital would not improve mortality in a New York state population. Caution should be used in extrapolating results of population based studies when healthcare systems are dissimilar,” they concluded.

Better outcomes from hypothermia in comatose with non-shockable initial rhythms

Comatose cardiac arrest patients with non-shockable initial rhythms who are treated with therapeutic hypothermia may have better survival and neurologic outcomes than those who do not receive hypothermic treatment, according to a retrospective cohort study.

Using 2000 to 2013 data from 16 institutions that contribute to the Penn Alliance for Therapeutic Hypothermia (PATH) registry, researchers simulated a randomized controlled trial using a propensity score to match 201 pairs of treated (with hypothermia) and control (no hypothermia) patients. Their mean age was 63±17 years, 51% were men, and 60% had an initial rhythm of pulseless electrical activity (PEA). Outcomes were survival rates and neurologic outcomes, defined by Cerebral Performance Category (CPC), at discharge. Results were published in the Dec. 1, 2015, Circulation.

In the propensity matched cohort, 29% of patients who underwent hypothermia survived to hospital discharge, compared to 15% who received standard care (P=0.001). In this same population, 21% of hypothermia patients survived to hospital discharge with a CPC 1 or 2 (“good” outcomes), versus 10% of the other patients (P=0.003). Adjusted analyses showed that patients who received hypothermia were more likely to survive (odds ratio [OR], 2.8, 95% CI, 1.6 to 4.7) and to have better neurologic outcomes (OR, 3.5, 95% CI, 1.8 to 6.6).Patients who underwent hypothermia were younger (62 vs. 69 years old, P<0.001), had longer durations of arrest (23 vs. 13 minutes, P<0.001), and had a higher incidence of asystole (vs. PEA) as their primary rhythm (45% vs. 35%, P<0.001). Hypothermia patients were also more likely to have had an out-of-hospital cardiac arrest (82% vs. 39%, P<0.001).

The researchers noted the limitations of their study, such as how the retrospective nature of the PATH data may have contributed to bias and how they did not account for other types of inpatient therapy, such as percutaneous coronary intervention, in their analyses. Patients with do-not-resuscitate or withdrawal-of-life-sustaining-therapy orders were excluded, possibly altering outcomes of both cohorts, they noted.

“Our findings provide further support for the use of [therapeutic hypothermia] in patients with initial non-shockable rhythms, given the lack of randomized controlled trial data, and should encourage its use in this patient population while awaiting data from randomized trials,” the study authors wrote.

Apixaban may prevent or shorten rehospitalizations for acute VTE

In patients with acute venous thromboembolism (VTE), use of apixaban was associated with significantly reduced all-cause hospitalizations compared to enoxaparin with warfarin, a study found.

Researchers used results from the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial to evaluate the effects of apixaban versus enoxaparin/warfarin on all-cause hospitalizations. The study was sponsored by drug manufacturers, and authors were employees of or consultants for those companies.

The AMPLIFY trial included adult patients with objectively confirmed symptomatic proximal deep venous thrombosis or pulmonary embolism who were enrolled between 2008 and 2012. Of the 5,365 patients, 2,676 were randomized to apixaban, 10 mg twice daily for the first 7 days followed by 5 mg twice daily for 23 weeks; the other 2,689 received enoxaparin, 1 mg/kg of body weight every 12 hours for at least 5 days, followed by warfarin, begun concomitantly, for 6 months. Results appeared Dec. 1, 2015, in the Journal of the American Heart Association.

Over the 6-month period, there were 182 all-cause hospitalizations (not including the index event) in the apixaban group and 218 in the enoxaparin/warfarin group. A significantly lower proportion of apixaban-treated patients had 1 or more hospitalizations compared with those treated with enoxaparin/warfarin (5.72% vs. 7.07%; hazard ratio [HR], 0.804; 95% CI, 0.650 to 0.995; P=0.045). Similar results were seen for hospitalizations in the first 30 days (2.28% in the apixaban group vs. 3.35% in the enoxaparin/warfarin group; HR, 0.676; 95% CI, 0.488 to 0.935; P=0.018).

The total length of stay for the hospitalizations was 1,535 days in the apixaban group compared to 2,197 days for those treated with enoxaparin/warfarin. The mean (SD) length of hospital stay per hospitalized patient was shorter with apixaban (10.2 [13.7] days vs. 11.7 [28.2] days). The median time to first hospitalization was longer for patients receiving apixaban than for those receiving enoxaparin/warfarin (63.0 days versus 34.5 days). The numbers of emergency department visits and rehabilitation unit admissions were similar in both treatment groups (P=0.631 and 0.692, respectively). There were significantly fewer doctor's office visits in apixaban-treated patients compared to enoxaparin/warfarin-treated patients (P=0.026).

The authors wrote that the estimated annual cost of VTE treatment was $2 billion in the United States in 2013, or $15.6 to $34.8 billion when considering complications, productivity loss, and other societal costs. Of these figures, hospitalizations and inpatient management of VTE account for more than half of total costs. “Therefore, taking both the AMPLIFY and AMPLIFY-EXT studies into account, the reduction in all-cause hospitalizations with apixaban versus enoxaparin/warfarin could lead to significant savings in the annual costs of VTE treatment,” the authors wrote.

CVP-guided hydration reduced risk of contrast nephropathy

Using central venous pressure (CVP) to guide IV hydration reduced contrast-induced nephropathy in patients with chronic kidney disease and heart failure undergoing coronary procedures, a Chinese study found.

The trial randomized 264 patients with kidney disease and heart failure to either standard hydration or guided hydration, in which the hydration infusion rate was adjusted every hour according to CVP level. Average estimated glomerular filtration rate was 36 mL/min/1.73m2 in the guided hydration group versus 39 mL/min/1.73m2 in the standard hydration group (P=0.224).

All of the patients were given 0.9% sodium chloride starting 6 hours before coronary angiography and continuing 12 hours afterward. Contrast-induced nephropathy was defined as an absolute increase in serum creatinine >0.5 mg/dL or a relative increase >25% of baseline.

The CVP group had a much lower rate of contrast-induced nephropathy than the standard hydration group: 15.9% vs. 29.5% (P=0.006). They also received significantly more fluid (mean of 1,827 mL vs. 1,202 mL) and had greater urine volume (1,461 mL vs. 806 mL). Major adverse events within 90 days of the procedure were lower in the CVP group than the control group (8.3% vs. 20.5%; P=0.004), and similar percentages of patients developed acute heart failure during hydration (3.8% vs. 3.0%). Results were published in the January JACC: Cardiovascular Interventions.

The study authors concluded that CVP-guided fluid administration can safely and effectively reduce the risk of contrast-induced nephropathy in patients with kidney disease and heart failure. They noted that such patients are at high risk of this complication but that aggressive volume expansion is not suitable for all high-risk patients, such as those with acute decompensated heart failure. There are a number of mechanisms by which volume expansion may reduce contrast-induced nephropathy, the authors said.

This intervention is one of a number of recent efforts to maximize hydration in patients at risk for contrast-induced nephropathy without sacrificing safety, according to an accompanying editorial. Other options include measuring left ventricular end diastolic pressure or using a forced diuresis system. “These results reaffirm the importance of giving as much IV fluid as possible,” the editorial said, noting that increasing hydration does not entirely eliminate contrast-induced nephropathy, so other novel therapies are needed.

Beta-blocker usage may reduce lactate levels in severe sepsis

In a recent study of severe sepsis, patients who had previously taken beta-blockers had lower blood lactate levels than similarly sick patients who hadn't taken beta-blockers, leading researchers to suspect that the drugs confound lactate measurement.

The retrospective cohort study included 260 patients with severe sepsis or septic shock, treated in a French emergency department. Twenty-five percent of them had previously been prescribed beta-blockers. Results were published in the December 2015 Critical Care Medicine.

The beta-blocker patients had an average blood lactate concentration of 3.9 mmol/L (SD, ±2.3 mmol/L), significantly lower than the 5.6 mmol/L (SD, ±3.6 mmol/L) in the other patients (P<0.001). The difference was still significant after researchers controlled for a number of factors, including mortality, severity (according to PIRO and SOFA scores), and source of infection. Blood lactate levels were normal in 21.5% of the beta-blocker patients versus 6.2% of the non-beta-blocker group (P=0.0008). Only 2 factors were found to be significantly and independently associated with normal blood lactate levels—survival and beta-blocker therapy.

The findings suggest that using blood lactate measurement as a triage tool in patients taking beta-blockers may underestimate the severity of sepsis, the study authors concluded. Clinicians should interpret lactate results in such patients with caution, they advised. The authors also noted that beta-blockers could further complicate sepsis triage by minimizing sepsis-induced tachycardia and making systemic inflammatory response syndrome-negative severe sepsis more likely.

The exact mechanisms of the findings are uncertain, and other research has been investigating whether beta-blocker therapy could have a beneficial effect on mortality in severe sepsis, the authors noted. This study did find a trend toward decreased mortality among the beta-blocker patients, but this was not a prespecified outcome and the difference was not significant, possibly due to small sample size.