Journal watch: Recent studies of note

Recent studies of note.


After heart surgery, greater mortality risk for frail patients

Frail patients are at higher risk after cardiac surgery of in-hospital mortality, discharge to an institution and lower midterm survival, a study found.

Researchers identified 3,826 patients undergoing surgery at a center in Nova Scotia between June 2004 and December 2007. Frailty was measured by deficiency in at least one of these measures: the Katz Index of Independence in Activities of Daily Living (ADL), independence of ambulation, and previous diagnosis of dementia. Primary outcomes were in-hospital death, midterm all-cause death (including in-hospital and post-discharge death) and institutional discharge. The study was published in the March 2 Circulation.

Of all patients, 4.1% were frail. Specifically, 1.7% had a deficiency in the Katz index of ADL, 3.2% had some degree of dependence in ambulation, and 0.6% had a previous dementia diagnosis. Among frail patients, 106 (67.5%) had a deficit in only one category, 49 (31.2%) had deficits in two categories and 2 (1.3%) had deficits in all three. In-hospital deaths within each frail category were 14.2%, 14.3% and 50%, respectively.

Frail patients were older (median age, 71 years vs. 66 years; P=0.0001), were more likely to be female, and had more comorbidities. In unadjusted analysis, frail patients had higher in-hospital mortality than the non-frail (14.7% vs. 4.5%; P<0.0001); by logistic regression analysis, frailty was an independent risk factor for in-hospital death (odds ratio [OR], 1.8; 95% CI, 1.1 to 3.0). Frailty also predicted institutional discharge (48.5% for frail patients vs. 9% for nonfrail; P<0.0001) in univariate analysis and by logistic regression analysis (OR, 6.3; 95% CI, 4.2 to 9.4). Frailty was an independent predictor of reduced midterm survival in regression analysis (hazard ratio, 1.5; 95% CI, 1.1 to 2.2) and univariate analysis (29.5% frail deaths vs. 10.6% nonfrail deaths; P<0.0001).

Before surgery, the frail patients were sicker and older, the authors noted. They were also more likely to undergo complex procedures, which may reflect a referral bias, with physicians not referring frail elderly patients for coronary artery bypass grafting unless they have an insurmountable disease burden, the authors noted. Study limitations include the single-center setting and retrospective nature. Overall, the results suggest that assessing frailty prior to surgery helps predict patients at highest risk for death and institutional discharge, the authors said. It also identifies patients who need to be more fully informed about risks of surgery, and who could potentially benefit from processes of care that offset the burden of frailty, they said.

Lower-than-standard dose of rt-PA just as effective for PTE

A lower dose of recombinant tissue-type plasminogen activator (rt-PA, alteplase) works as well as the standard dose in treating pulmonary thromboembolism (PTE), and may carry fewer risks, a study found.

In a prospective, randomized, multicenter trial, Chinese researchers assigned 65 patients to receive 50 mg of rt-PA over two hours, and 53 patients to receive 100 mg over two hours. Patients had acute PTE and either hemodynamic instability or massive pulmonary artery obstruction and right ventricular dysfunction (RVD). Researchers measured efficacy by observing improvements in RVDs on echocardiograms, lung perfusion defects on ventilation perfusion lung scans, and pulmonary artery obstructions on CT angiograms. They also measured death, bleeding and PTE recurrence. Results were reported in the February Chest.

Patients in both groups saw similar improvements in right ventricular dysfunctions, lung perfusion defects, and pulmonary artery obstructions, regardless of whether they had hemodynamic instability or massive pulmonary artery obstruction. Six percent of patients (n=3) died in the 100 mg/2 hour rt-PA group and 2% (n=1) died in the 50 mg/2 hour rt-PA group due to PTE or bleeding. The 50 mg/2 hour rt-PA patients with a body weight of less than 65 kg were significantly less likely to have bleeding episodes than the 100 mg/2 hour patients of the same weight category (14.8% vs 41.2%, P=0.049). Neither group had fatal recurrent PTE.

Study limitations included a small sample size, and the fact that physicians treating patients were not blinded to the study. The study results emphasize the importance of finding the optimal rt-PA dose when treating patients with PTE, given the risk of bleeding with the treatment, the authors noted. An editorialist noted that imaging showed 11% of 50 mg patients deteriorated compared to 4% of 100 mg patients; skeptics may say that such worsening is the outcome to be most concerned with, the editorialist wrote. Still, while the results aren't definitive, physicians should consider using the 50 mg/2 hour dose in lower-weight patients with PE who have hemodynamic compromise or another indication for thrombolysis, the editorialist said.

Negative cultures found in 55% of patients treated for sepsis

More than half of patients admitted and treated for severe sepsis had negative culture results for the infection, a study found.

In a prospective, observational study, researchers enrolled 211 patients from November 2005 through October 2007 from an urban teaching hospital in North Carolina. Included patients had suspected infection, two or more systemic inflammatory response syndrome criteria and hypoperfusion; patients were excluded who needed immediate surgery or were younger than age 18. ED physicians and staff identified patients, started the resuscitation protocol, placed the central venous catheter and followed the protocol until an ICU bed was available. Blinded observers used a priori definitions to distinguish the final reason for hospitalization. The study was published online February 9 in Clinical Infectious Diseases.

Forty-five percent of patients were positive by culture; 55% were negative by culture. Methicillin-resistant Staphylococcus aureus accounted for 18% of bacteremia episodes. Culture-positive patients were more likely to have indwelling vascular lines (19% vs. 9%, P=0.03), be nursing home residents (25% vs. 14%, P=0.04), have an active malignancy (22% vs. 11%, P=0.04) and have a shorter time to antibiotic administration (83 minutes vs 97 minutes, P=0.03).

There were no significant differences in the severity of illness between the groups. Of culture-negative patients, 52% had clinical infections or atypical infections. Thirty-two percent of culture-negative patients had noninfectious mimics; the most common of these diagnoses were inflammatory colitis, hypovolemia, medication effects, adrenal insufficiency, acute myocardial infarction, and acute pulmonary embolus. The cause of illness was indeterminate or multifactorial in 16% of culture-negative patients.

Eighteen percent of patients who were identified as having sepsis had noninfectious diagnoses that mimicked sepsis—some of which require urgent alternate treatment, the authors noted. There was no statistically significant difference in the classic indicators of infection, abnormal temperature and white blood cell count, between the culture-positive and culture-negative groups. Because pneumonia accounted for 55% of the final infectious etiologies in the culture-negative group, physicians should consider workup for pneumonia in patients who have negative cultures for sepsis and suspected infection, the authors said. Since there is no single test that allows for inclusion or exclusion of sepsis, physicians should continue to consider other etiologies in undifferentiated patients, even if they have already begun treatment for sepsis, they added.

Limitations include that the study was at a single center and was not conducted as a tightly controlled experiment; thus, results may not be generalizable. A larger sample may have yielded different incidence of alternate disease etiologies as well, the authors noted.

Hyponatremia linked to mortality, longer stays, discharge to care facilities

Hyponatremia causes more mortality, longer stays and more discharges to care facilities regardless of whether it's community-acquired, hospital-aggravated or hospital-acquired, a study found.

Researchers reviewed all adult hospitalizations at St. Elizabeth's Medical Center, a 400-bed acute care tertiary hospital in Boston, between October 2000 and September 2007, for which an admission serum sodium concentration ([Na+]) was available (n=53,236 admissions among 29,904 patients). They reported their results in the Feb. 8 Archives of Internal Medicine.

They defined community-acquired hyponatremia as an admission serum [Na+] less than 138 mEq/L, hospital-aggravated as a drop of at least 2 mEq/L during the first 48 hours of hospitalization and hospital-acquired as a serum [Na+] less than 138 mEq/L after a normal admission serum.

Community-acquired hyponatremia occurred in 20,181 hospitalizations (37.9%). These patients were older, had a higher comorbidity score, and were more likely to be admitted to medical services. Community-acquired hyponatremia was associated with in-hospital mortality (3.4% vs 2.0%; odds ratio [OR], 1.52; 95% CI, 1.36 to 1.69), discharge to a short- or long-term care facility (OR, 1.12; 95% CI, 1.08 to 1.17) and a longer stay (adjusted increase, 14%; 95% CI, 11% to 16%).

Hospital-aggravated hyponatremia occurred in 1,151 hospitalizations (5.7%). It was independently associated with a higher risk of in-hospital mortality (OR, 2.30; 95% CI, 1.75 to 3.02), compared to community-acquired hyponatremia with no further decline (OR 1.46; 95% CI, 1.31 to 1.64).

Hospital-acquired hyponatremia developed in 10,662 (38.2%) of hospitalizations longer than one day. These patients were older, more likely to be admitted to surgical services and more likely to have a higher comorbidity score. Hospital-acquired hyponatremia was associated with more in-hospital mortality (2.9% vs 1.4%; OR, 1.66; 95% CI, 1.39 to 1.98), discharge to a care facility (OR, 1.64; 95% CI, 1.55 to 1.74), and a longer stay (64%; 95% CI, 60% to 68%). This relationship was observed for mild cases where serum [Na+] was 133 to 137 mEq/L (OR, 1.31; 95% CI, 1.08 to 1.58), and it progressively strengthened with worsening hyponatremia.

When serum [Na+] was evaluated as a continuous variable, the adjusted risk of death increased by 23% for each 1-mEq/L decline below 138 mEq/L (OR, 1.23; 95% CI, 1.19 to 1.27).

Although 135 to 145 mEq/L is frequently used as the reference range for serum [Na+], the study found mortality increased when values declined below 138 mEq/L or increased above 142 mEq/L. Even serum [Na+] values slightly below normal (133 to 137 mEq/L) were independently associated with mortality, prolonged length of stay and discharge to a facility. But more studies in other centers and in a variety of clinical settings would be required before changing the current reference range, the authors said.

In considering the underlying mechanisms between any association, researchers wrote, “Whether the relationship between hyponatremia and adverse outcomes is causal or associative, hyponatremia is a compelling prognostic marker of adverse outcomes. The identification of even mild hyponatremia should compel physicians to exercise heightened vigilance.”