Recent Research

Therapy for decompensated heart failure with cardiorenal syndrome, kidney measures for CKD, and more.


Ultrafiltration inferior to diuretics for decompensated HF with cardiorenal syndrome

Ultrafiltration did not improve outcomes for patients with decompensated heart failure and cardiorenal syndrome compared to pharmacological therapy, according to a recent study.

Researchers randomized 188 patients hospitalized with acute decompensated heart failure, worsened renal function and persistent congestion to either stepped pharmacological therapy (an algorithm involving continuous infusion of diuretics with the addition of metolazone, vasoactive therapy or both) or ultrafiltration. Change in serum creatinine level and body weight was assessed at 96 hours, and patients were followed for 60 days.

After 96 hours, the ultrafiltration group had an increase in serum creatinine of 0.23 ± 0.70 mg/dL (20.3 ± 61.9 µmol/L) while the pharmacologic group had a slight decrease: −0.04 ± 0.53 mg/dL (−3.5 ± 46.9 µmol/L) (P=0.003). The groups lost similar amounts of weight in the 96 hours (5.5 ± 5.1 kg on pharmacology vs. 5.7 ± 3.9 on ultrafiltration; P=0.58). The ultrafiltration group had a higher percentage of serious adverse events (72% vs. 57%; P=0.03), leading study authors to conclude that ultrafiltration was inferior to pharmacologic therapy for these endpoints.

In longer-term follow-up, the groups also had similar rates of weight loss, mortality and rehospitalization for heart failure in the next 60 days. “Given the high cost and complexity of ultrafiltration, the use of this technique as performed in the current study does not seem justified for patients hospitalized for acute decompensated heart failure, worsened renal function and persistent congestion,” the authors concluded.

The results, which appeared in the Dec. 13, 2012 New England Journal of Medicine, challenge current understandings about ultrafiltration, according to an accompanying editorial. The findings on creatinine levels are particularly surprising and hard to explain. Researchers and clinicians will have to continue searching for better strategies for these patients, who have dismal outcomes overall, with more than a third dying or being readmitted within 60 days, the editorial said. It's possible, the editorialist noted, that ultrafiltration may need to be used more slowly.

“We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences,” the editorialist concluded.

Kidney measures for CKD predict clinical risk across the full age range, study suggests

Measures of kidney function used to diagnose and stage chronic kidney disease (CKD) are independently associated with end-stage renal disease (ESRD) and mortality regardless of age, according to a recent study.

Researchers performed an individual-level meta-analysis of over two million people to determine whether age modified the association of estimated glomerular filtration rate (eGFR) and albuminuria with ESRD and death. Both relative and absolute risks were evaluated. The meta-analysis looked at hazard ratios (HRs) of the primary end points, all-cause mortality and ESRD, according to eGFR and albuminuria by age category; data were adjusted for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol level, body mass index and smoking status. HRs and average incidence rates were used to determine absolute risks. The study results were published in the Dec. 12, 2012 Journal of the American Medical Association.

Participants from the Chronic Kidney Disease Prognosis Consortium, which is made up of 33 general population cohorts and 13 CKD cohorts in Asia, Australasia, Europe and North and South America, were included. Patients were followed for a mean of 5.8 years between 1972-2011. The mean patient age was 49.4 years, and 7.3% of patients were older than age 75. Deaths (112,325 people) and ESRD (8,411 events) were higher in patients with lower eGFR and higher albuminuria in every age category. In both general and high-risk cohorts, relative mortality risk decreased with increasing age for reduced eGFR (adjusted HRs, 3.50 [95% CI, 2.55 to 4.81], 2.21 [95% CI, 2.02 to 2.41], 1.59 [95% CI, 1.42 to 1.77], and 1.35 [95% CI, 1.23 to 1.48] for an eGFR of 45 mL/min/1.73 m2 vs. 80 mL/min/1.73 m2 in patients age 18 to 54 years, 55 to 64 years, 65 to 74 years, and ≥75 years, respectively; P<0.05 for age interaction). Absolute risk differences increased with age for the same comparisons (9.0 excess deaths per 1,000 person-years [95% CI, 6.0 to 12.8], 12.2 excess deaths per 1,000 person-years [95% CI, 10.3 to 14.3], 13.3 excess deaths per 1,000 person-years [95% CI, 9.0 to 18.6], and 27.2 excess deaths per 1,000 person-years [95% CI, 13.5 to 45.5], respectively).

Reduced relative risk with increasing age was less marked for increased albuminuria. However, absolute risk differences were higher by older age category: 7.5 excess deaths per 1,000 person-years (95% CI, 4.3 to 11.9), 12.2 excess deaths per 1,000 person-years (95% CI, 7.9 to 17.6), 22.7 excess deaths per 1,000 person-years (95% CI, 15.3 to 31.6), and 34.3 excess deaths per 1,000 person-years (95% CI, 19.5 to 52.4), respectively, for an albumin-creatinine ratio of 300 mg/g compared with 10 mg/g. Adjusted relative hazards of mortality did not decrease with age in cohorts of patients with CKD, and in all cohorts, relative risks and absolute risk differences for ESRD at lower eGFRs or higher albuminuria values were comparable by age.

The authors noted that serum creatinine measurements were not standardized among studies, that no gold standard exists for measuring urine albumin, that the cohorts were heterogeneous, and that their results are based on models adjusted for traditional risk factors and therefore require careful interpretation. However, they concluded, “Although some variation in management of CKD should be considered by age based on cost and benefits, with respect to risk of mortality and ESRD, our data support a common definition and staggering of CKD based on eGFR and albuminuria for all age groups.”

The author of an accompanying editorial wrote that older adults with CKD are at high risk for death, usually from cardiovascular disease, and that clinicians should make every effort to offer proven treatment strategies in this population. “Preventing progression of CKD may be an important goal in some patients, but most older patients with CKD will not progress to ESRD,” the author wrote. He also stressed that some treatments that are effective in middle-aged adults with normal kidneys may have different benefits and risks, especially drug-related adverse effects, in older patients. “To move forward,” he wrote, “CKD identification must be coupled with new treatment strategies tailored to patients with CKD, including older patients with CKD.”

Stroke risk higher up to 12 weeks after hip replacement, study finds

Risk for stroke is elevated up to 12 weeks after total hip replacement, according to a recent study.

Researchers in Denmark performed a nationwide cohort study to determine the timing of stroke after total hip replacement surgery. Patients who had had a primary total hip replacement were matched by age, sex and region with three controls who had not had total hip or knee replacement surgery. The effects of comorbid conditions and medications on the timing of stroke were also assessed. The study results were published in the December 2012 Stroke.

A total of 66,583 patients and 199,995 controls were included in the study. Mean age in both groups was 71.9 years, and most of the study population (63.1%) was female. Previous use of cardiovascular drugs was slightly more likely and prevalence of previous cerebrovascular disease was modestly higher in total hip replacement patients than controls, while use of pain relievers was substantially higher. Compared with matched controls, patients who had total hip replacement had a 4.7-fold increased risk for ischemic stroke and a 4.4-fold increased risk of hemorrhagic stroke in the first two weeks after surgery. This elevated risk persisted for a total of six weeks and 12 weeks, respectively. Risk for ischemic stroke was 70% lower in patients who took antiplatelet agents after hospital discharge. Statistical power was too low to detect significant effect modification for hemorrhagic stroke.

The authors noted that they did not have data available on body mass index, which may affect stroke risk, or on use of antithrombotic agents during hospitalization, among other limitations. However, they concluded that risk for ischemic and hemorrhagic stroke appeared to be elevated for at least six and at least 12 weeks, respectively, after total hip replacement and that risk assessment for stroke in individual patients undergoing this procedure should be considered during this time period. Although use of antiplatelet therapy appeared to substantially lower postoperative risk for ischemic stroke, the authors wrote that “this seemingly protective effect should be interpreted with caution, given the observational design and the lack of information on inpatient antithrombotic use.”

Registry appears to improve survival, neurologic outcomes after in-hospital cardiac arrest

Survival and neurologic outcomes after in-hospital cardiac arrest have improved at hospitals participating in the Get with the Guidelines—Resuscitation registry, according to a recent study.

Researchers looked at data from adults who had a cardiac arrest at any of 374 hospitals participating in the Get with the Guidelines—Resuscitation registry between 2000 and 2009. Temporal trends in risk-adjusted rates of survival to discharge were analyzed, and causes and relation to neurologic disability were examined. The study results appeared in the Nov. 15, 2012 New England Journal of Medicine.

A total of 84,625 patients had a cardiac arrest in the hospital, and 14,357 (17%) survived until discharge. Overall, 79.3% initially had asystole or pulseless electrical activity and 20.7% had ventricular fibrillation or pulseless ventricular tachycardia. Over time, the proportion of cardiac arrests related to asystole or pulseless electrical activity increased (68.7% in 2000 vs. 82.4% in 2009; P<0.001 for trend), as did risk-adjusted rates of survival to discharge (13.7% in 2000 vs. 22.3% in 2009; adjusted rate ratio per year, 1.04; P<0.001 for trend). Acute and postresuscitation survival improved in both rhythm groups, leading to similar overall improvements in survival. Clinically significant neurologic disability decreased over time (risk-adjusted rate, 32.9% in 2000 vs. 28.1% in 2009; adjusted rate ratio per year, 0.98; P=0.02 for trend).

The authors noted that residual confounding could have affected their results and that data on specific processes and treatments were not available, among other limitations. However, they concluded that both survival to hospital discharge and rates of clinically significant neurologic disability after in-hospital cardiac arrest have improved in hospitals participating in Get with the Guidelines—Resuscitation. The authors estimated that based on their findings, an additional 17,200 patients survived to discharge in 2009 compared with 2000 and that over 13,000 cases of neurological disability were similarly avoided. They called for future studies to determine which specific factors led to the improvements so that they can be applied in all hospitals.

Same mortality risk with saline, hydroxyethyl starch for ICU fluid resuscitation

For fluid resuscitation in the intensive care unit (ICU), hydroxyethyl starch (HES) and saline carry the same mortality risk, but the former is associated with greater need for renal replacement therapy, a study found.

Researchers randomly assigned 7,000 ICU patients to receive either 0.9% sodium chloride (saline), or 6% HES with a molecular weight of 130 kD and a molar substitution ratio of 0.4 (130/0.4, Voluven) in 0.9% saline. These were used for all fluid resuscitation until death, ICU discharge or 90 days post-randomization. The main outcome was death within 90 days, and secondary outcomes were acute kidney injury and failure, and treatment with renal replacement therapy. Predefined subgroups for the main outcome included, at baseline, presence or absence of diagnostic criteria for urine output for acute kidney injury, presence/absence of sepsis, presence/absence of trauma with or without traumatic brain injury, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and receipt/ nonreceipt of HES before randomization. Results were published in the Nov. 15, 2012 New England Journal of Medicine.

Death rates were similar in both groups (18% in HES group vs. 17% in saline group; relative risk [RR], 1.06; P=0.26), as were lengths of stay in the hospital or ICU and time on mechanical ventilation. Mortality was also similar in the six subgroups. Seven percent of the HES group and 5.8% of the saline group required renal replacement therapy (RR, 1.21; P=0.04). Renal injury occurred more often in the saline group than the HES group (38% vs. 34.6%; P=0.005), but there was no significant difference in renal failure between groups. Incidence of new cardiovascular organ failure was significantly lower in the HES group (36.5% vs. 39.9%, RR, 0.91; P=0.03), while new hepatic organ failure was higher (1.9% vs. 1.2%; RR, 1.56; P=0.03). Overall, HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001), with pruritus and rash being the most common ones.

The results don't support resuscitation with 6% HES (130/0.4) compared with saline in the ICU, especially since it led to an increased rate of renal replacement therapy, the authors noted. “The selection of resuscitation fluid in critically ill patients requires careful consideration of its safety, its potential effect on patient-centered outcomes, and its cost,” they concluded.

Antishivering drugs have varying efficacy, review finds

To treat shivering in inpatients, several drugs have been studied and found efficacious, but data is insufficient to label any one the best, a recent review concluded.

Researchers identified 80 publications with 119 randomized, double-blinded, placebo-controlled substudies of antishivering medications in their review, and they calculated the risk benefit and number needed to treat of the five most frequently studied and most efficacious medications. The data suggested high efficacy for three medications: meperidine (risk ratio, 2.2; number needed to treat, 2), tramadol (risk ratio, 2.2; number needed to treat, 2) and nefopam (risk ratio, 2.1; number needed to treat, 2). However, nefopam is not available in the U.S. at all, and tramadol is not available in the intravenous formulation used in the studies.

Drugs in the modest efficacy category included ketamine (risk ratio, 1.8; number needed to treat, 3) and clonidine (risk ratio, 1.6; number needed to treat, 4), as well as dexmedetomidine, granisetron, physostigmine and magnesium sulfate. However, clonidine was also administered in its non-U.S. intravenous formulation. The reviewers also assessed the drugs by class and concluded that centrally acting analgesics, opioid receptor agonists, cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists were more effective than α2-central agonists, antiserotonergics and anti-inflammatory drugs.

There was significant heterogeneity among the randomized controlled trials, the researchers noted, and only 70% of them used objective shivering outcome measures. Most of the studies also failed to track side effects of the medication in a standardized way. Given the limitations of the analysis, “no final conclusion as to what is the ‘best’ antishivering medication should be drawn,” the authors said. Results were published in the November 2012 Critical Care Medicine.

The authors additionally noted that the studied medications may have different activity with different administration routes and goals (such as treatment vs. prophylaxis). Several of the studies also assessed combined medication regimens, but not enough data was available to draw conclusions on these treatment options.

Central line bundle reduced infections across hospital systems

A multi-faceted intervention to reduce central line-associated bloodstream infections (CLABSIs) proved to be sustainable and replicable in a recent trial.

Researchers conducted a randomized trial in 45 intensive care units in 35 hospitals from two health systems. The tested intervention included the CLABSI-prevention bundle developed by the Johns Hopkins Quality and Safety Research Group: hand washing before line placement; using full barrier precautions; avoiding line placement at the femoral site; using chlorhexidine to cleanse the site; and removing unnecessary lines. They added to this a culture-change intervention, the Comprehensive Unit-based Safety Program, which included training about systems and safety, collaboration with hospital executives, and efforts to improve teamwork and communication.

Results appeared in the November 2012 Critical Care Medicine.

One of the hospital systems implemented the intervention beginning in March 2007. The other served as a control group until October 2007, when it began the intervention. At baseline, CLABSI rates were 4.48 per 1,000 central line days in the intervention group and 2.71 per 1,000 in the control group. By October-December 2007, the intervention group's infection rate had declined to 1.33, compared to 2.16 in the control group (P=0.003). The intervention group's rate decreased further and was sustained below 1 per 1,000 even 19 months after the intervention. The control group, once it began the intervention, also reduced rates below 1 per 1,000 and had sustained them at 12 months.

The study is the first randomized, controlled trial of such a combined bundle/culture change effort to reduce CLABSI, the authors said. The participating hospitals successfully replicated (and actually improved on) the results of the Keystone project, providing further proof that most CLABSI infections are preventable. It's also significant that the project was nurse-led, confirming nurses' role as logical leaders of such interdisciplinary safety programs. However, in interviews about the intervention process, nurses reported that more physician engagement would have been beneficial.

Lower tidal volumes in ventilation linked to better outcomes for non-ARDS patients

For patients receiving ventilation who didn't have acute respiratory distress syndrome (ARDS), using lower tidal volumes was associated with improved outcomes, a meta-analysis found.

Researchers searched several databases for studies that evaluated use of lower vs. higher tidal volumes at the start of mechanical ventilation in patients without ARDS. Development of lung injury was the primary endpoint, and secondary endpoints were mortality, pulmonary infection, atelectasis, intensive care unit (ICU) and hospital length of stay, time to extubation, change in Paco2, arterial pH values, and change in the ratio of Pao2 to fraction of inspired oxygen. Results were published in the Oct. 24, 2012 Journal of the American Medical Association.

In the 20 studies that qualified for analysis, a fixed-effects model showed a decrease in lung injury development in patients who received ventilation at lower tidal volumes (4.22% vs. 12.66%; risk ratio [RR], 0.33; number needed to treat [NNT], 11) and in mortality (RR, 0.64; NNT, 23). Results for lung injury were similar when stratified by type of study, either randomized or nonrandomized. Lower tidal volumes were associated with significantly less pulmonary infection only in randomized trials, and with significantly lower mortality only in nonrandomized trials. A random effects model showed that lower tidal volume also was associated with shorter mean hospital length of stay (6.91 vs. 8.87 days, respectively), higher mean Paco2 levels (41.05 vs. 37.90 mm Hg), and lower mean pH values (7.37 vs. 7.40), but similar mean ratios of Pao2 to fraction of inspired oxygen (304.40 vs. 312.97).

An important limitation of the analysis is that, in most of the studies, patients received ventilation for a relatively short time, which makes it complicated to generalize the results to patients who are ventilated for long periods in the ICU, the authors noted. Also, they noted that all the dichotomous analyses except for pulmonary infection yielded results that showed no heterogeneity, but all the continuous analyses showed significant heterogeneity. “Clinical trials are needed to compare higher vs. lower tidal volumes in a heterogeneous group of patients receiving mechanical ventilation for longer periods,” the authors concluded.

Zolpidem linked to greater inpatient fall risk

Inpatients taking zolpidem are significantly more likely to fall than those not taking the drug, a recent study found.

In a retrospective cohort study, researchers analyzed records of 16,320 patients admitted to Mayo Clinic hospitals in 2010 who were prescribed zolpidem, usually on an as-needed basis. Pregnant and ICU patients were excluded. Researchers compared outcomes of the 4,962 (30.4%) patients who actually took the prescribed zolpidem to those of the 11,358 patients (69.6%) who were prescribed the drug but didn't take it. At Mayo hospitals, clinicians must report all falls to a central event reporting system, and researchers used this system to obtain details of inpatient falls in 2010. Results were published online Nov. 19, 2012 by the Journal of Hospital Medicine.

Patients who were prescribed and took zolpidem had a significantly higher fall rate than those who were prescribed the drug but didn't take it (3.04% vs. 0.71%; P<0.001). Zolpidem remained significantly associated with higher fall risk when researchers accounted for gender, age, zolpidem dose, insomnia, delirium status, Hendrich's fall risk score, comorbidities, length of stay, and several other factors (adjusted odds ratio, 4.37; P<0.001). Patients who took zolpidem were older (P<0.001), more likely to be male, and more likely to have insomnia and delirium than those who were prescribed the drug but didn't take it. Patients who took zolpidem also had a higher risk of falling compared to a group of all adult inpatients—including those not prescribed the drug at all. The number needed to harm for patients receiving zolpidem was 55.

Past research in healthy volunteers has shown zolpidem is associated with greater difficulty maintaining balance, the authors wrote. This tendency may be worse in a hospital setting, which is a novel environment to the patient; as well, the inpatient may be taking other medications that impact balance, they wrote. Still, use of other balance-compromising medications didn't differ between those who took zolpidem and those who didn't. Thus, zolpidem does appear to increase fall risk beyond what can be attributed to other medications, they wrote.

Hospitals should consider changing order sets so zolpidem use isn't encouraged, the authors said. Facilities could also try using fall precautions in patients prescribed zolpidem, or use non-drug treatments for insomnia, though these interventions still need to be empirically tested, the authors wrote.

Citicoline no better than placebo for traumatic brain injury patients

Citicoline didn't improve functional and cognitive status of patients with traumatic brain injury when compared to placebo after 90 days of treatment, a study found.

In a double-blind, randomized trial, researchers studied outcomes of 1,213 patients with traumatic brain injury (TBI) at eight level-one trauma centers in the U.S. between July 20, 2007 and Feb. 4, 2011. All patients—who had TBI classified as complicated mild, moderate or severe—underwent 90 days of daily oral or enteral citicoline (2,000 mg), or placebo. Treatment was initiated within 24 hours of injury. Functional and cognitive status was assessed using the TBI-Clinical Trials Network Core Battery, and a global statistical test was used to analyze the nine scales of the battery. For secondary outcomes, researchers assessed functional and cognitive improvement at 30, 90 and 180 days. Results were published online Nov. 21, 2012 by the Journal of the American Medical Association.

The citicoline and placebo groups didn't differ significantly in outcomes at 90 days (global odds ratio [OR], 0.98). There were also no significant differences in outcomes by treatment within the subgroups of complicated mild (OR, 0.89) and moderate/severe TBI (OR, 1.14). Patients with moderate/severe TBI also had no statistically significant difference by treatment group at the 180-day evaluation, though patients with complicated mild TBI in the placebo group did better than their peers in the citicoline group (global OR, 0.72; P=0.004) at 180 days. The proportion of patients who reported serious adverse events didn't differ between treatment groups.

The study suggests citicoline isn't superior to placebo in patients with a range of TBI severity, and it use should be questioned in patients with TBI, the authors concluded. Further, citicoline may have a negative effect on longer-term (180 days) recovery for patients with complicated mild TBI, they noted. Editorialists agreed the study “conclusively demonstrated the lack of efficacy of citicoline monotherapy for TBI,” adding that the broader implication may be that no single agent is adequate to improve functional outcomes for these patients. “The diverse and complex nature of the pathological mechanisms activated by TBI suggests that multimodal treatment interventions may be needed to improve recovery,” and future research should examine these, they wrote.

Six months of warfarin associated with better survival after prosthetic valve surgery

Warfarin therapy after bioprosthetic aortic valve replacement was associated with reduced rates of thromboembolic events and mortality, a recent study found.

Researchers used data on more than 4,000 patients from the Danish National Patient Registry who had surgical aortic valve replacement (AVR) with biological prostheses in 1997-2009. The study looked at whether warfarin was prescribed, and if so, when the prescription was discontinued. The mean follow-up was 6.57 years. Results were published in the Nov. 28, 2012 Journal of the American Medical Association.

Patients who took warfarin had significantly lower risk of stroke (2.69 per 100 person-years vs. 7 per 100 person-years; adjusted incidence rate ratio [IRR], 2.46) and thromboembolic events (3.97 vs. 13.07 per 100 person-years; IRR, 2.93) than those who were not taking it. The warfarin group also had fewer cardiovascular deaths: The comparison was 3.83 versus 31.74 per 100 person-years (IRR, 7.61) for deaths 30 to 89 days after surgery and 2.08 versus 6.50 per 100 person-years (IRR, 3.51) for deaths 90 to 179 days after surgery.

The results demonstrate a clear benefit to using warfarin during the initial three months after surgery and suggest a benefit from extending therapy to six months, the study authors concluded. They noted that their study was limited by lack of data about time in therapeutic achieved international normalized ratios and potential confounding by comorbidities, but given these results and the lack of randomized data, they called for review of existing guidelines to consider the extension of warfarin treatment for patients receiving bioprosthetic AVR.

Current guidelines on this question are conflicting, noted an accompanying editorial. The American College of Cardiology/ American Heart Association (ACC/AHA) and European Society of Cardiology recommend three months of warfarin, and the ACC/AHA recommends adding aspirin. The American College of Chest Physicians recommends aspirin alone unless there are other risk factors such as atrial fibrillation. This study does not resolve the dilemma of whether to use aspirin (or the emerging option of novel oral anticoagulants), but it should change warfarin prescribing practices, the editorialist concluded, noting that “the optimal duration of therapy appears to be 6 months.”

Digoxin associated with higher mortality in afib patients

Digoxin was associated with a significant increase in all-cause mortality in patients with atrial fibrillation, regardless of gender and whether they had had heart failure, a study found.

To determine the relationship between digoxin and mortality in patients with atrial fibrillation, researchers assessed patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure, as defined by a history of heart failure and/or an ejection fraction less than 40%. Results appeared online Nov. 27, 2012 in the European Heart Journal.

Digoxin was associated with an increase in all-cause mortality (estimated hazard ratio [EHR], 1.41; P<0.001), cardiovascular mortality (EHR, 1.35; P=0.016), and arrhythmic mortality (EHR, 1.61; P=0.009). The all-cause mortality was increased with digoxin in patients without or with heart failure (EHR, 1.37; P=0.019 and EHR, 1.41; P=0.010, respectively). There was no significant interaction between digoxin and gender for all-cause (P=0.70) or cardiovascular (P=0.95) mortality.

All-cause mortality was 41% higher in patients with heart failure and 37% higher in patients without heart failure. These findings call into question the widespread use of digoxin in patients with atrial fibrillation, researchers wrote. Recent studies put its use at between 35% and 70% of these patients, despite limited safety data and controversy over its use. The authors noted several limitations to the study, including lack of data on serum digoxin level and kidney function.

Benzodiazepines associated with community-acquired pneumonia

Benzodiazepines are associated with risk for and death from community-acquired pneumonia (CAP), according to a recent study.

Researchers in the United Kingdom performed a nested case-control study of data from the Health Improvement Network, a database of primary care patients, to determine whether an association existed between CAP and therapy with benzodiazepines. They hypothesized that benzodiazepines might increase CAP risk because of their potential effects on immune function. The authors also examined the effects of zopiclone, a nonbenzodiazepine that has a similar mechanism of action. The study's primary end points were risk of CAP and mortality from CAP at 30 days and over the long term, a median follow-up of 2.8 years. The study results were published online on Dec. 5, 2012 by Thorax.

A total of 4,964 cases and 29,697 controls were included in the study. Cases were patients whose medical records indicated a diagnosis of pneumonia between July 1, 2001 and July 1, 2002. Approximately 54% of both cases and controls were women. The authors used conditional logistic regression to detect an association between drug use and CAP and then used Cox regression to determine the drugs' effects on mortality among the 4,964 cases.

An association was found between benzodiazepine use and increased pneumonia risk (odds ratio, 1.54; 95% CI, 1.45 to 1.67) and between use of diazepam, lorazepam or temazepam and increased CAP incidence. No such individual association was seen with chlordiazepoxide, but an increased risk was also associated with zopiclone. Thirty-day mortality (hazard ratio, 1.22; 95% CI, 1.06 to 1.39) and long-term mortality (hazard ratio, 1.32; 95% CI, 1.19 to 1.47) appeared to be higher in patients with CAP who had taken benzodiazepines. Each of the four benzodiazepines studied also appeared to individually affect long-term mortality, but zopiclone did not. Only diazepam and lorazepam appeared to individually affect 30-day mortality.

The authors noted that unmeasured confounders and selection bias may have affected their results and that their findings do not prove a cause-and-effect relationship between benzodiazepines and CAP, among other limitations. However, they concluded that benzodiazepines and zopiclone appear to be associated with higher risk for and death from CAP. “Given the widespread use of benzodiazepine drugs,” they wrote, “further studies are required to evaluate their safety in the context of infection.”

Screening, treating asymptomatic bacteriuria before surgery not beneficial

Screening and treatment for asymptomatic bacteriuria before surgery wasn't associated with benefit in a new study.

Researchers at the Minneapolis VA Medical Center identified all orthopedic, cardiothoracic and vascular surgical procedures at their center in fiscal year 2010 (1,934 procedures in 1,688 patients, 96% of whom were men), and abstracted data on any preoperative urine culture or result in the seven days before each procedure. For results, they labeled bacteriuria as high-count if there were ≥100,000 colony-forming units (CFUs)/mL and low-count if there were 10,000 to 90,000 CFU/mL. Results with fewer than 10,000 CFU/mL were considered negative for bacteriuria. The researchers also assessed complications including allergies, diarrhea, Clostridium difficile (C. diff) infection and surgical site infections (SSIs). Results were published online Dec. 3, 2012 in a research letter by Archives of Internal Medicine.

Urine cultures were obtained before 25% of procedures, and this practice varied significantly by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%; P<0.001), though not by type of procedure. Screened patients were older, more frequently male, and more likely to develop SSIs, diarrhea and C. diff infection. Eleven percent of all cultures revealed bacteriuria. Detection of high-count bacteriuria (5%) varied by service (orthopedic, 13%; vascular, 8%; cardiothoracic, 1%; P<0.001), but low-count detection didn't. Postoperative urinary tract infections were more frequent among patients with bacteriuria than those without (9% vs. 2%; P<0.01), but there were no differences in SSIs, diarrhea, C. diff infections or allergies based on culture result. Among the 54 patients who tested positive for bacteriuria, those who were treated with antimicrobials were more likely to develop an SSI (45% vs. 14%; P=0.03)—a result that “may be confounded by factors that contributed to the decision to administer antimicrobial drugs,” the authors wrote.

Preoperative urine cultures were ordered inconsistently, the findings were rarely positive for bacteriuria, and when bacteriuria was detected, it was usually not treated, the authors noted. The results, however, did come from small samples of an observational study and should be interpreted cautiously due to the potential for confounding, they wrote. Still, they concluded that, outside the context of a clinical trial, clinicians should avoid preoperative screening for and treatment of asymptomatic bacteriuria in patients slated for orthopedic, cardiothoracic or vascular surgery.

An editorialist was more equivocal, however, writing that “given the few treated patients and the strong likelihood of confounding variables, this study cannot provide conclusive evidence about the risks and benefits of treating preoperative bacteriuria in older men,” but it does “call into question current treatment practices concerning bacteriuria in men.”