Fluid balance, MI rule-out, anticoagulation after hemorrhage, and more

Summaries from ACP Hospitalist Weekly.

Negative, positive vs. even fluid balance may increase long-term mortality risk among critically ill, study finds

Both positive and negative fluid balance, compared to even fluid balance, were associated with higher long-term mortality risk in a recent study of critically ill patients.

Using an ICU database from one large academic medical center, researchers examined the association between positive and negative fluid balance, compared with even fluid balance, and long-term renal recovery in 18,084 adult patients admitted from July 2000 through October 2008.

Researchers determined cumulative fluid balance from ICU admission until the end of the index ICU stay or until initiation of renal replacement therapy (RRT), whichever came sooner. The primary outcomes were time to mortality from the index ICU admission (up to one year) and renal recovery (defined as alive and independent from RRT at one year).

Results were published online on April 21 by Critical Care Medicine and appear in the August issue.

Acute kidney injury developed in 15,229 patients (84%), and 1,545 patients (8.5%) received RRT. The distribution of negative, even, and positive fluid balance was about 26.6%, 28.2%, and 45.3% of patients, respectively.

Positive fluid balance, compared with even fluid balance, was associated with one-year mortality in the logistic regression analysis (adjusted odds ratio [OR], 1.72; 95% CI, 1.55 to 1.92). Using Gray's model, it was associated with highest mortality risk within the first 178 days after ICU admission (adjusted hazard ratio [HR] range, 1.61 to 1.92). The association was attenuated over time but persisted up to 365 days (P<0.001).

Negative fluid balance, compared with even fluid balance, was not associated with mortality in the logistic regression analysis (adjusted OR, 1.067; 95% CI, 0.94 to 1.21). However, using Gray's model, negative fluid balance was associated with lower mortality up to 11 days after ICU admission (adjusted HR, 0.81; 95% CI, 0.68 to 0.96) but with higher mortality between 88 and 365 days after ICU admission (adjusted HRs, 1.16 [95% CI, 1.01 to 1.32] for days 88 to 178 and 1.22 [95% CI, 1.05 to 1.42] for days 178 to 365).

Neither negative nor positive fluid balance was associated with renal recovery among patients who received RRT. However, the mortality risk associated with positive fluid balance decreased with use of RRT (adjusted HR range for interaction, 0.43 to 0.89; P<0.001).

The study authors noted limitations, such as the study's observational nature and that they calculated fluid balance only during ICU admission and not from charting in the ED or ward. They added that the single-center design may affect the generalizability of the results.

The authors stated that their findings have implications for clinical care, such as the current use of negative fluid balance as a justification for liberating patients early from mechanical ventilation. “[T]he long-term consequences of such recommendations are unclear,” they wrote.

EKG and high-sensitivity troponin T may rule out myocardial infarction

A single measurement of high-sensitivity cardiac troponin T and an electrocardiogram (EKG) may rule out acute myocardial infarction (AMI) in ED patients, according to a recent meta-analysis.

Researchers included 11 cohort studies with 9,241 patients who presented to the ED with possible acute coronary syndrome and received an EKG and measurement of high-sensitivity cardiac troponin T. The primary outcome was AMI during hospitalization and secondary outcomes were major adverse cardiac events (MACE) or death within 30 days. Results were published April 18 by Annals of Internal Medicine and appear in the May 16 issue.

Image by Thinkstock
Image by Thinkstock

Patients were classified as low risk if they had no new ischemia on EKG and the troponin measurement was below 0.005 µg/L; 30.6% of the study patients fell into this category. An AMI occurred during hospitalization in 0.5% of these patients. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in the studies, with a pooled estimate of 98.7% (95% CI, 96.6% to 99.5%). None of the low-risk patients died and sensitivity for MACE within 30 days ranged from 87.9% to 100% in the studies, with a pooled sensitivity of 98.0% (95% CI, 94.7% to 99.3%).

“Integrating such an early screening approach into existing investigative strategies may enable patients to be safely discharged to outpatient follow-up earlier than in current practice,” the authors said. However, they noted several caveats, including that the rule-out strategy showed much lower sensitivity in two of the included study cohorts than in the others, “which could indicate that the strategy is not universally safe.”

It's also known that troponin may not be detectable immediately after myocardial injury, so this strategy would not be recommended for patients presenting within three hours of symptom onset, the authors said. The results also only apply to the studied assay, not any future troponin T assays. The specificity of this strategy is low, so it should not be used to rule in AMI or to identify patients at high risk.

Future research should combine this rule-out strategy with assessment of risk factors and symptoms, the authors suggested. “The incorporation of risk and symptoms may reassure physicians of the safety of the early rule-out strategy, although possibly at the risk of lower efficacy,” they wrote. Hospitals that decide to implement the rule-out strategy should also conduct local audits to ensure safety and efficacy, they advised.

Restarting anticoagulation after intracerebral hemorrhage associated with lower thromboembolic risk

Restarting anticoagulant therapy after intracerebral hemorrhage (ICH) may be associated with lower risk for thromboembolic complications with no change in ICH recurrence risk, according to a recent study.

Researchers performed a systematic review and meta-analysis of cohort studies in adults with ICH associated with anticoagulation to determine whether resuming therapy was associated with risk for ICH recurrence and thromboembolic events. The latter were defined as stroke or myocardial infarction. Included studies were published through Sept. 30, 2016, and involved nontraumatic ICH as the primary inclusion criterion; outcomes of ischemic stroke, myocardial infarction, and ICH recurrence during follow-up; clear documentation of whether anticoagulation was restarted after ICH; and at least 10 adult patients 18 years of age or older. Study results were published online April 17 by Stroke.

Eight studies of 5,306 patients with ICH were included in the meta-analysis. All involved anticoagulation with oral vitamin K antagonists, with the exception of one study in which some patients received novel oral anticoagulants. Six studies involving 2,044 patients were included in the analysis of thromboembolic events after ICH; the remaining two studies focused on recurrence of ICH. Mean patient age for all studies ranged from 69 to 78 years, and most patients were men. Most patients had been receiving anticoagulation before ICH for atrial fibrillation (34.7% to 77.8%), with the next most common reasons being prosthetic heart valve (2.6% to 27.8%), venous thromboembolism (7.9% to 20.8%), and previous ischemic stroke (3.7% to 71.8%).

In the six studies included in the analysis of thromboembolic events after ICH, 38.4% of patients had anticoagulation restarted. A total of 6.7% of those on anticoagulation after ICH had a thromboembolic event compared with 17.6% of those not on anticoagulation. Restarting anticoagulation was associated with lower risk for thromboembolic complications, with a pooled relative risk of 0.34 (95% CI, 0.25 to 0.45; P=0.28 for heterogeneity). In the eight studies analyzed for an association between anticoagulation and ICH recurrence, 35.8% of patients had anticoagulation restarted after ICH. ICH recurred in 8.7% of patients who were receiving anticoagulation and 7.8% of those who were not. Although substantial heterogeneity was seen among the studies, risk for ICH recurrence did not appear to be associated with resumption of anticoagulant therapy (pooled relative risk, 1.01; 95% CI, 0.58 to 1.77; P<0.001 for heterogeneity).

The authors noted that they found no randomized trials examining this issue in the literature, that the selection criteria of the included studies varied, and that they could not determine why anticoagulation was or was not reinstituted after ICH, among other limitations. However, they concluded that their review and meta-analysis showed an association between restarting anticoagulation after ICH and lower risk for thromboembolic complications, with a similar risk for ICH recurrence. “Randomized clinical trials are needed to determine the true risk-benefit profile of anticoagulation resumption after ICH,” the authors wrote. In the absence of such trials, they said, their results could help guide clinicians in informed decision making.

New drug for acute heart failure failed to improve inpatient symptoms or long-term mortality

Ularitide, an intravenous synthetic form of the renal vasodilatory natriuretic peptide urodilatin, did not improve mortality among patients with acute heart failure, a recent trial found.

The double-blind, industry-funded trial randomized 2,157 patients with acute heart failure to a continuous IV infusion of 15 ng per kg of body weight of ularitide or placebo for 48 hours in addition to usual care. Treatment was initiated a median of six hours after evaluation. Results were published online April 12 by the New England Journal of Medicine and appear in the May 18 issue.

Primary outcomes were death from cardiovascular causes (with a median follow-up of 15 months) and a composite measure of a patient's clinical course during the 48 hours of treatment. The composite was measured at three points during the infusion and included vital status (alive or dead), investigator documentation of persistent or worsening heart failure requiring prespecified interventions, and a patient global assessment.

Rates of cardiovascular death during follow-up were similar between groups (21.7% on ularitide vs. 21.0% on placebo) and an intention-to-treat analysis found no significant difference in the composite 48-hour outcome. The ularitide group did have greater reductions in systolic blood pressure and N-terminal pro-brain natriuretic peptide, but no significant difference in changes in cardiac troponin T levels. Researchers concluded that ularitide exerted favorable physiological effects, but that it did not affect the primary outcomes of the study. In addition to not proving effectiveness of the drug, the study “raises doubt about theories that early ventricular distention causes myocardial necrosis and adversely affects the natural history of heart failure after hospitalization and that rapid reversal of short-term ventricular distention preserves myocardial viability,” the study authors said.

An accompanying editorial agreed, noting that “we do not have a mandate to establish rapid-response teams for patients who present with acute decompensated heart failure.” He added that the study's negative findings should lead physicians to “remind ourselves that the primary immediate objective of treatment is the patient-centric goal of symptom relief.”