Journal watch: Recent studies of note

Kidney decline and mortality in acute severe hypertension, and more.

Kidney decline associated with higher mortality in patients with acute severe hypertension

Patients hospitalized for acute severe hypertension should be closely monitored for signs of renal dysfunction, as even subtle changes can increase patients' risk of death, a recent study found.

Researchers compared data on patients with severe hypertension (one or more blood pressure measurements ≥180 mm Hg systolic and/or ≥110 mm Hg diastolic and treated with intravenous antihypertensive therapy) enrolled in the Studying the Treatment of Acute Hypertension registry. Seventy-nine percent of the cohort had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Patients with acute kidney injury (AKI) were at higher risk than other patients of heart failure and cardiac arrest and had a higher mortality rate at 90 days. The study was published May 25 in Circulation.

Any acute loss of kidney function during hospitalization was independently associated with an increased risk of death. The study is the first to show that even a subtle decline in kidney function in patients with severe hypertension triggers increased risk of death, as well as acute heart failure, cardiac arrest and bleeding episodes. The risk progressively increases as AKI becomes more severe, the authors said. The findings highlight the importance of monitoring patients closely for kidney decline as patients who develop severe AKI may show no clinical signs at admission besides elevated creatinine concentration.

The study highlights the need for novel markers of AKI (analogous to cardiac troponins) that would identify high-risk patients on admission, the authors said. Such markers should lead to novel treatment strategies that lower blood pressure and improve renal and cardiac outcomes.

Three processes of care associated with improved outcomes after stroke

Attention to swallowing function, deep vein thrombosis (DVT) prophylaxis, and treatment of hypoxia are independently associated with improved outcomes for stroke and transient ischemic attack (TIA) patients, a recent study found.

In a retrospective cohort study, researchers studied 1,487 adult patients admitted to one of five hospitals with an acute ischemic stroke or TIA who had neurologic symptom onset no more than two days before admission and a score ≥2 on the National Institutes of Health Stroke Scale. They then evaluated seven established processes of acute stroke care: neurological evaluation, swallowing evaluation, DVT prophylaxis, early mobilization, blood pressure management, fever management and hypoxia management. The combined outcome included in-hospital mortality, discharge to hospice or discharge to a skilled nursing facility. The study period was 1998-2003. Results were published in the May 10 Archives of Internal Medicine.

Among the patients studied, 92% had a definitive stroke, 2% had definitive TIA, 2% had a stroke vs. TIA and 4% had a probable stroke or TIA. Sixteen percent of patients had the combined outcome; 6% died in the hospital. Neurologic worsening or death was seen in 14% of patients.

Prevalence of individual processes of care ranged from 29% receiving treatment for all episodes of fever, to 92% receiving a neurological evaluation. After adjusting for the other processes of care and the risk adjustment score, the processes of care independently associated with a reduction in the combined outcome were: swallowing evaluation (adjusted odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43-0.94), DVT prophylaxis (adjusted OR, 0.60; 95% CI, 0.37-0.96), and treating all episodes of hypoxia with supplemental oxygen (adjusted OR, 0.26; 95% CI, 0.09-0.73).

All medical facilities could successfully implement these three processes of care, since sophisticated structures aren't needed to do so, the authors said. While hypoxia treatment isn't a current performance measure, clinicians and organizations should consider focusing on it, along with swallowing evaluation and DVT prophylaxis, they added.

Treating STEMI beyond recommended time increases mortality

Treating ST-elevation myocardial infarction (STEMI) patients with reperfusion therapy beyond the recommended treatment times may increase mortality and readmission risk, a recent study found.

Treatment guidelines specify a maximum delay of 30 minutes for fibrinolysis and 90 minutes for primary percutaneous coronary intervention (PPCI) for STEMI patients. Researchers evaluated care for 1,832 STEMI patients treated with reperfusion during a six-month period in 2006-2007 in 80 hospitals in Quebec, Canada. Main outcome measures were death at 30 days and one year, and a combined end point of death or hospital readmission for acute myocardial infarction (MI) or congestive heart failure at one year. Results were published June 2 in the Journal of the American Medical Association.

Twenty-one percent of patients (n=392) received fibrinolysis and 79% (n=1,440) received PPCI. Fibrinolysis was untimely (given after more than 30 minutes) in 54% of patients, and PPCI was untimely (given after 90 minutes) in 68% of patients. When the treatment groups were combined, patients treated beyond the recommended times had a higher adjusted risk of death at 30 days (6.6% vs. 3.3%; odds ratio [OR], 2.14; 95% CI, 1.21 to 3.93) than the patients who got timely treatment. Those treated beyond recommended times also had an adjusted higher risk for the combined outcome of death or hospital readmission for acute MI or congestive heart failure at one year (15% vs. 9.2%; OR, 1.57; 95% CI, 1.08 to 2.30).

The study is robust in that it represents “not a sampling, but 95% of STEMI patients within a large and complex system of care,” the authors noted. It was also undertaken in a single-payer, universal access system, and thus associations aren't likely to be confounded by socioeconomic or insurance differences, they added. The association between longer treatment delay and poorer outcome may be confounded, they said, because patients who are sicker may be treated later; they may, for example, require more time to be hemodynamically stabilized. Overall, the findings suggest that time to reperfusion, rather than strategy, is more important for outcomes, which can help inform clinical decision making in the future, the authors said.

High-frequency oscillation may improve survival in ARDS patients vs. ventilation

When compared to conventional mechanical ventilation, high-frequency oscillation may improve survival in patients with acute lung injury and acute respiratory distress syndrome (ARDS), a recent meta-analysis found.

Researchers analyzed data from eight randomized controlled trials with a total of 419 patients, almost all of whom had ARDS. In-hospital or 30-day mortality was the primary outcome; secondary outcomes included six-month mortality, duration of mechanical ventilation, ventilator-free days to day 28 or 30, health-related quality of life at one year, and treatment failure leading to crossover to the other arm or discontinuation of the study protocol. The authors also considered various adverse events, including barotrauma and hypotension, and the following physiological outcomes measured at 24, 48 and 72 hours after randomization: oxygenation, oxygenation index, ventilation and mean airway pressure. The article was published May 18 by BMJ.

In-hospital and 30-day mortality was significantly lower for patients assigned to high-frequency oscillation versus conventional ventilation (risk ratio [RR], 0.77; 95% CI, 0.61 to 0.98; P=0.03). Oscillation patients were also less likely to experience treatment failure such as refractory hypoxemia, hypercapnia, hypotension or barotraumas that resulted in discontinuation of therapy (RR, 0.67; 95% CI, 0.46 to 0.99; P=0.04). The ratio of partial pressure of oxygen to inspired fraction of oxygen was also 16% to 24% higher in oscillation patients at 24, 48 and 72 hours. There were no significant differences in oxygenation index, as mean airway pressure rose by 22% to 33% in patients receiving oscillation (P≤0.01). There was also no difference between groups in the duration of mechanical ventilation, or in frequency of adverse events.

Study limitations include that the primary analysis of mortality was based on relatively few patients and had wide confidence intervals; also, the control groups in three studies were exposed to higher-than-recommended tidal volumes. The definition of treatment failure also varied across trials, and data were limited such that certain analyses weren't possible (such as duration of ventilation for survivors vs. non-survivors). While more trials are needed, physicians who “currently use or are considering high-frequency oscillation to treat ARDS can be reassured by these results,” the authors concluded.

Post-heart attack hyperoxia associated with increased in-hospital mortality

Hyperoxia is associated with higher in-hospital mortality compared to hypoxia or normoxia among patients admitted to intensive care units (ICUs) after resuscitation from cardiac arrest, researchers found.

Researchers conducted a multicenter cohort study using a critical care database of 131 U.S. hospitals between 2001 and 2005. The hospitals contributing to the study (n=120) comprised multiple types of ICUs and varied by size and geography.

Patient inclusion criteria were age 17 years or older, nontraumatic cardiac arrest, cardiopulmonary resuscitation within 24 hours prior to ICU arrival, and arterial blood gas analysis performed within 24 hours of arrival. Patients were categorized by the first arterial blood gas values obtained in the ICU: hyperoxia (PaO2 of 300 mm Hg or greater), hypoxia (<60 mm Hg or ratio of PaO2 to fraction of inspired oxygen <300), and normoxia (neither hyperoxia or hypoxia). Results appeared in the June 2 Journal of the American Medical Association.

Of 6,326 patients, 1,156 (18%) had hyperoxia, 3,999 (63%) had hypoxia, and 1,171 (19%) had normoxia. Overall, 56% of patients (n=3,561) died in the hospital. The hyperoxia group had significantly higher in-hospital mortality (732 of 1,156 [63%; 95% CI, 60% to 66%]) compared with the normoxia group (532 of 1,171 [45%; 95% CI, 43% to 48%]; proportion difference, 18% [95% CI, 14% to 22%; P<0.001]) and the hypoxia group (2297 of 3,999 [57%; 95% CI, 56% to 59%]; proportion difference, 6% [95% CI, 3% to 9%]; P<0.001). After researchers controlled for potential confounders such as age, preadmission functional status, comorbidity or vital signs, hyperoxia had an odds ratio (OR) for death of 1.8 (95% CI, 1.5 to 2.2).

Further, patients with hyperoxia were proportionally less likely to be discharged as functionally independent compared with patients with normoxia (29% vs. 38%, respectively; proportion difference, 9% [95% CI, 3% to 15%]; P=0.002). Multivariable logistic regression analysis factors significantly associated with in-hospital death included age, nonindependent functional status prior to admission, emergency department origin, active chemotherapy, chronic renal failure, hypotension on ICU arrival, tachycardia and hypoxia.

A secondary analysis that defined hyperoxia as PaO2 400 mm Hg or greater found higher mortality (377 of 549; 69% [95% CI, 65% to 72%]) compared with the hypoxia group (2,297 of 3,999; 57% [95% CI, 56% to 59%]) and normoxia group (887 of 1,778; 50% [95% CI, 48% to 52%]). This hyperoxia group had significantly higher in-hospital mortality compared with the normoxia group (proportion difference, 19% [95% CI, 14% to 24%]; P<0.001). Mortality also was significantly higher in the hyperoxia group compared with the hypoxia group (proportion difference, 12% [95% CI, 8% to 16%]; P<0.001).

Replacing peripheral IV catheters routinely may not be necessary

There is no conclusive evidence that changing peripheral intravenous (IV) catheters routinely reduces the risk of phlebitis and bacteremia, according to a review.

The Centers for Disease Control and Prevention guidelines recommend replacing peripheral IV catheters every 72 to 96 hours, with an eye toward reducing bacteremia and phlebitis, the authors noted. To see if the measure is effective, they examined randomized controlled trials that compared routine removal with removal that occurred only when clinically indicated, in hospitalized or community-dwelling patients who were receiving intermittent or continuous infusions. Results were published in Issue 3, 2010 of the Cochrane Database of Systemic Reviews.

In five trials (3,408 subjects), there was a non-significant 44% reduction in suspected catheter-related bacteremia in the clinically indicated group (odds ratio [OR], 0.57; 95% CI, 0.17 to 1.94; P=0.37). In six trials (3,455 patients), there also was no significant difference in phlebitis between groups (9% for clinically indicated group vs. 7.2% for routine group; P=0.09). In addition, there was no difference in phlebitis incidence per 1,000 device days. In two trials (961 patients), cannulation costs were significantly lower in the clinically indicated group (mean difference, −6.21; 95% CI −9.32 to −3.11; P<0.000).

Given that the review found no conclusive evidence of benefit to routinely changing IV catheters, health care facilities may consider a policy of changing catheters only when it appears necessary. Not only would this provide cost savings, it “would also be welcomed by patients, who would be spared the unnecessary pain of routine re-sites in the absence of clinical indications,” the authors wrote.

Inpatients with acute MI face risk of hospital-acquired anemia

Almost half of patients hospitalized with acute myocardial infarction (MI) who receive percutaneous coronary intervention (PCI) or medical therapy develop hospital-acquired anemia (HAA) during their stay, a recent study found.

Using the TRIUMPH registry, researchers identified patients with acute MI and normal hemoglobin on admission. Patients were excluded from the study if they underwent coronary artery bypass grafting (CABG) during the index admission because anemia is very common after CABG, and because post-CABG outcomes differ from those of patients treated with PCI or medications. Patients were also excluded if they didn't survive to discharge, or had chronic anemia at admission; this left a study population of 2,909 patients. Results appeared in the July Circulation: Cardiovascular Quality and Outcomes.

Forty-five percent of patients had HAA at discharge, with 26% of those patients having moderate-severe HAA (defined as hemoglobin <11 g/dL). While in-hospital bleeding was more common in patients with HAA compared to those without HAA, 86.5% of patients with HAA didn't have any documented in-hospital bleeding. Significant, independent correlates of HAA included female sex, older age, white race, chronic kidney disease, ST-segment elevation myocardial infarction, acute renal failure, use of glycoprotein IIb/IIIa inhibitors, length of stay, and in-hospital complications including cardiogenic shock, bleeding and bleeding severity. After adjustment for bleeding and GRACE (Global Registry of Acute Coronary Events) scores, patients with moderate-severe HAA had higher mortality rates (hazard ratio [HR], 1.82; 95% CI, 1.11 to 2.98, compared to no HAA), and had poorer health status at one year. Health status was measured via the Short Form-12 Physical Component Summary score (SF-12 PCS).

Since most patients with HAA didn't have documented bleeding during their stay, HAA probably isn't a surrogate for in-hospital bleeding events, the authors noted. Because of the association of moderate-severe HAA with a higher mortality risk, HAA would seem to be “prognostically important in its own right, and may represent a target for prevention efforts,” the authors wrote. HAA rates varied widely across hospital sites, suggesting the risk of developing it could indeed be minimized, they added.

Preoperative statins protect elective abdominal aortic aneurysm patients

Preoperative statin therapy has a protective effect on patients who undergo elective abdominal aortic aneurysm (AAA) repair, and may also lower total hospital costs, a recent study found.

In a retrospective review, researchers used a computerized database to identify 401 patients with infrarenal AAAs who had undergone elective, nonruptured open (OAR) or endovascular repair (EVAR) between July 2004 and July 2007. Preoperative and procedural variables were also collected from patient records, and included perioperative medical management. Outcomes included inpatient or 30-day mortality, myocardial infarction, renal failure, stroke, pneumonia, urinary tract infection, wound complication, estimated blood loss from anesthesia record, length of stay, postoperative stay, and total hospital cost. Results were published in the June issue of the Journal of Vascular Surgery.

EVAR patients who received statins had significantly fewer postoperative days compared to EVAR patients who didn't receive statins (1.9 ± 0.2 days vs. 2.3 days ± 0.3 days, P<0.05), despite having a higher Society for Vascular Surgery risk score. The EVAR statin cohort also had a shorter hospital length of stay (2.3 ± 0.3 days vs. 2.8 ± 0.4 days, P<0.05). Among OAR patients, the statin cohort had fewer postoperative complications (4.4% vs. 14.7% for non-statin cohort, P<0.05) and a lower mortality rate (0% vs. 5.9%, P<0.05). Statin therapy also reduced total cost per EVAR patient by $3,205 and total cost per OAR patient by $3,792 (P<0.05).

Study limitations include the fact that the data were drawn from a single institution and collected retrospectively. There was also a relatively small number of patients in the analysis, making the risk of statistical error significant, the authors wrote. Still, based on the data, the authors now initiate statin therapy for elective AAA repair patients at the initial consultation, and continue it through the surgery until the first postoperative visit, where they recommend continuing the medication with the primary care physician, they said. “We recommend statin therapy as an essential component in the preoperative regimen for all patients undergoing elective AAA repair,” the authors wrote.

Medication adherence better with low-molecular-weight heparin than unfractionated heparin

Hospitalized patients were more likely to adhere to a medication regimen of once-daily low-molecular-weight heparin (LMWH) than a regimen of unfractionated heparin (UFH) twice or three times daily, a study found.

Researchers queried the medication records at Brigham and Women's Hospital in Boston, in which nurses document the reasons that doses aren't given or are delayed. They identified 250 consecutive patients who were prescribed prophylaxis with LMWH once daily, or UFH two or three times daily, and followed patients' adherence throughout their hospitalization. Adherence was defined as the ratio of doses given to doses ordered. Results were published in the June issue of The American Journal of Medicine.

Patients taking LMWH had 94.9% adherence compared to those taking UFH three times daily (87.8% adherence) or UFH twice daily (86.8% adherence; P<0.001). Patients taking LMWH were also more likely to receive all scheduled prophylaxis doses (77%) compared to those taking UFH three times daily (54%) or UFH twice daily (45%) (P<0.001). Reasons for omitting doses didn't differ by regimen, with patient refusal being the most common reason for late or skipped doses. Forty-four percent of the UFH orders, and 39% of the LMWH orders, weren't administered due to patient refusal.

Fear, anxiety, discomfort and inconvenience might lead patients to refuse injection-based prophylaxis, the solution to which may be novel anticoagulants with oral dosing, the authors noted. Patients also may refuse because they don't understand their risk factors for venous thromboembolism, which could be helped by improved communication between hospital providers and patients, as well as hospital-based patient education efforts, they said. The study's limitations include its single-center design and the possibility that nurses gave incorrect reasons for missed doses, the authors wrote.