Potential medical impact of unrecognized in vitro hypokalemia due to hemolysis: a case series.

OBJECTIVES: The destruction of red cells during blood collection or with the processing of the sample continues to occur at a high rate, especially among emergency department (ED) patients. This can produce pre-analytical laboratory errors, particularly for potassium. We determined the incidence of hemolyzed samples and discuss the potential medical impact for hypokalemic patients who potassium level is artificially normal (pseudoeukalemia). METHODS: Potassium results were obtained for a 6-month period. Using a measured hemolysis index (HI), hemolysis was present in 3.1 % for all potassium ordered (n=94,783) and 7.5 % for ED orders (n=22,770). Most of these samples were reported as having high normal result or were hyperkalemic. There were 22 hemolytic samples with a potassium of <3.5 mmol/L, and 57 hemolytic samples with a potassium in lower limit of normal (3.5-3.8 mmol/L). From this group, we examined the medical histories of 8 selected patients whose initially normal potassium levels were subsequently confirmed to have a potassium values that were below, at, or just above the lower limit of normal due to hemolysis. RESULTS: The primary complaint for these patients were: necrotizing soft tissue infection, pancreatitis, volume overload from heart failure with reduced ejection fraction, hypertension treated with hydrochlorothiazide, and presence of a short bowel syndrome. A subsequent non-hemolyzed sample was collected demonstrating hypokalemia in all of these patients. Within these cases, there was a potential for harm had hemolysis detection not been performed. CONCLUSIONS: We demonstrate the medical importance of detecting hemolysis for patients who have pseudoeukalemia. This is relevant because the HI cannot be obtained when electrolytes are tested using whole blood samples, and a normal potassium may lead to inappropriate patient management.

Multiple Cardiac Biomarker Testing Among Patients With Acute Dyspnea From the ICON-RELOADED Study.

BACKGROUND: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown. METHODS AND RESULTS: Concentrations of NT-proBNP, high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 were analyzed in 1448 patients presenting with acute dyspnea from the prospective, multicenter International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all 3 biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in 2 biomarkers (18.8%, 44 of 234), 1 biomarker (3.8%, 10 of 260), or no elevated biomarkers (0.4%, 2 of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite end point of mortality and HF rehospitalization. In adjusted models, patients with one, 2, and 3 elevated biomarkers had 3.74 (95% confidence interval [CI], 1.26-11.1, P = .017), 12.3 (95% CI, 4.60-32.9, P < .001), and 12.6 (95% CI, 4.54-35.0, P < .001) fold increased risk of 180-day mortality or HF rehospitalization. CONCLUSIONS: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic, and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.

On-Field Rule Out of Mild Traumatic Brain Injury: Can Blood-Based Biomarker Testing Change Outcome of Major Sporting Events?

BACKGROUND: Mild traumatic brain injury (mTBI) is defined as a Glascow Coma Score of between 13 and 15. The diagnosis and rule out of individuals suffering from mTBI on an acute basis is imperfect and involves subjective measures. Serum biomarkers that exhibit narrow within-individual biological variation can be used for the early rule-out of mTBI, when baseline levels are compared during health. METHODS: This is a descriptive study that applies published biological variation data of serum mTBI biomarkers for early rule out of sports-related injury. RESULTS: Laboratory tests such as glial fibrillary acidic protein, fatty acid binding protein 7, and phosphorylated protein enriched in astrocytes have low within-individual variances and are potential candidates. Aldolase C also rises early in blood but the biological variation is of this marker is currently unknown. CONCLUSIONS: The use of blood-based biomarkers, measured in real time using point-of-care testing devices when compared to a pre-competition baseline instead of a population-based reference interval, can provide early rule out of mTBI, and possibly enable on-field evaluations and a medical decision for a return to competition.

Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry.

The optimal use of diuretics in decompensated heart failure remains uncertain. We analyzed data from the ADHERE registry to look at the impact of diuretic dosing. 62,866 patients receiving <160 mg and 19,674 patients > or =160 mg of furosemide were analyzed. The patients receiving the lower doses had a lower risk for in-hospital mortality, ICU stay, prolonged hospitalization, or adverse renal effects. These findings suggest that future studies should evaluate strategies for minimizing exposure to high doses of diuretics.

N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study.

BACKGROUND: Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. OBJECTIVES: This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. METHODS: Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF. RESULTS: Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13). CONCLUSIONS: In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.

Prolonged emergency department stays of non-ST-segment-elevation myocardial infarction patients are associated with worse adherence to the American College of Cardiology/American Heart Association guidelines for management and increased adverse events.

STUDY OBJECTIVE: We evaluate the association of emergency department (ED) length of stay with use of guideline-recommended therapies for acute treatments and clinical outcomes. Prolonged ED stays often reflect ED crowding or limited hospital capacity. We hypothesized that patients with non-ST-segment-elevation myocardial infarction who have ED stays of greater than 8 hours may have lower quality of care and worse outcomes. METHODS: Using a secondary analysis of data from an observational registry (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines, CRUSADE), we compared rates of use of 5 individual acute (<24 hours) guideline-recommended therapies in patients with non-ST-segment-elevation myocardial infarction according to ED length of stay. Patients were grouped by length of stay (short [<4 hours], average [4 to 8 hours], or long [>8 hours]). Multivariable analyses were used to determine independent association of ED length of stay with acute medications and inhospital outcomes (death and myocardial infarction). RESULTS: This analysis included 42,780 patients with non-ST-segment-elevation myocardial infarction. The median ED length of stay was 4.3 hours (25th to 75th percentile 2.9, 6.3); 15% of patients stayed longer than 8 hours. Patients who had long ED stays were more likely to be women and nonwhite and less likely to have health maintenance organization or private insurance. After adjustment, patients with long ED stays less often received guideline-recommended acute myocardial infarction therapies. Although risk-adjusted inhospital mortality rates were similar among groups, the rate of recurrent myocardial infarction increased among patients with long ED stays (odds ratio 1.23; 95% confidence interval 1.01 to 1.48) compared with those with average ED length of stay. CONCLUSION: For patients with non-ST-segment-elevation myocardial infarction, long ED stays were associated with decreased use of guideline-recommended therapies and a higher risk of recurrent myocardial infarction. However, there was no observed difference in mortality. Factors associated with prolonged ED length of stay should be evaluated to optimize treatments and outcomes of patients with non-ST-segment-elevation myocardial infarction.

The role of cardiac risk factor burden in diagnosing acute coronary syndromes in the emergency department setting.

STUDY OBJECTIVE: We seek to determine whether cardiac risk factor burden (defined as the number of conventional cardiac risk factors present) is useful for the diagnosis of acute coronary syndromes in the emergency department (ED) setting. METHODS: This was a post hoc analysis of the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS) registry, which had 17,713 ED visits for suspected acute coronary syndromes. First visit for US patients who were not cocaine or amphetamine users, who did not leave against medical advice, and for whom ECG and demographic data were complete were included. Acute coronary syndrome was defined by 30-day revascularization, diagnostic-related group codes, or death within 30 days, with positive cardiac biomarkers at index hospitalization. Cardiac risk factors were diabetes, hypertension, smoking, hypercholesterolemia, and family history of coronary artery disease. Cardiac risk factor burden was defined as the number of risk factors present. Because multiple logistic regression analysis revealed that age modified the relationship between cardiac risk factor burden and acute coronary syndromes, a stratified analysis was performed for 3 age categories: younger than 40, 40 to 65, and older than 65 years. Positive likelihood ratios and negative likelihood ratios with their 95% confidence intervals (CIs) were calculated for each total risk factor cutoff. RESULTS: Of 10,806 eligible patients, 871 (8.1%) had acute coronary syndromes. In patients younger than 40 years, having no risk factors had a negative likelihood ratio of 0.17 (95% CI 0.04 to 0.66), and having 4 or more risk factors had a positive likelihood ratio of 7.39 (95% CI 3.09 to 17.67). In patients between 40 and 65 years of age, having no risk factors had a negative likelihood ratio of 0.53 (95% CI 0.40 to 0.71), and having 4 or more risk factors had a positive likelihood ratio of 2.13 (95% CI 1.66 to 2.73). In patients older than 65 years, having no risk factors had a negative likelihood ratio of 0.96 (95% CI 0.74 to 1.23), and having 4 or more risk factors had a positive likelihood ratio of 1.09 (95% CI 0.64 to 1.62). CONCLUSION: Cardiac risk factor burden has limited clinical value in diagnosing acute coronary syndromes in the ED setting, especially in patients older than 40 years.

Elevated serum cardiac markers predict coronary artery disease in patients with a history of heart failure who present with chest pain: insights from the i*trACS registry.

The significance of a history of heart failure (HF) in patients presenting with acute coronary syndromes and elevated cardiac markers is unclear. The authors performed an analysis of patients enrolled in the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS). Cardiac marker measurement and cardiac catheterization were performed in 1174 patients. Of these, 116 (9.9%) had heart failure (HF). Coronary artery disease (CAD) was found in 61 (52.6%) patients in the HF group and 581 (54.9%) in the group without HF. In the non-HF cohort, positive markers occurred in 306 patients, in whom 217 (70.9%) had CAD at catheterization. In the HF subset, 24 patients had positive biomarkers and 15 (62.5%) had CAD. A history of HF did not lessen the likelihood of CAD as evidenced by angiography and does not diminish the utility of cardiac markers in diagnosing acute coronary syndromes.

Discordant cardiac biomarkers: frequency and outcomes in emergency department patients with chest pain.

STUDY OBJECTIVE: We evaluate associations between pairs of discordant cardiac biomarkers (positive MB band of creatine kinase [CKMB] with negative creatine kinase, positive CKMB with negative cardiac troponin, and positive troponin with negative CKMB) and the presence of acute coronary syndromes in emergency department (ED) chest pain patients. METHODS: This was a secondary analysis of a prospective registry. Data were obtained from the multicenter Internet Tracking Registry of Acute Coronary Syndromes, which included 17,713 ED visits for possible acute coronary syndrome between June 1999 and August 2001. First visits and first ED cardiac biomarker results from the 9 sites, 8 in the United States and 1 in Singapore, were included. Subjects were excluded for incomplete information or an initial ECG consistent with ST-segment elevation myocardial infarction. Acute coronary syndrome was defined by diagnosis-related group code indicating myocardial infarction, positive invasive or noninvasive diagnostic testing, revascularization, or death during hospitalization or within 30 days. RESULTS: Of 8,769 eligible patients, 1,614 (18.4%) had acute coronary syndrome. The CKMB and cardiac troponin results were discordant in 7% of patients (CKMB+/cardiac troponin-, 4.9%, CKMB-/cardiac troponin+ 2.1%), whereas increased CKMB with normal creatine kinase levels occurred in 239 (3.1%) patients. The unadjusted odds ratios with 95% confidence intervals for acute coronary syndrome in patients with and without discordant markers were: CKMB+/CK- 5.7 (4.4-7.4), CKMB+/CK+ 4.4 (3.6-5.2), CKMB-/cTn+ 4.8 (3.4-6.8), CKMB+/cTn- 2.2 (1.7-2.8), CKMB+/cTn+ 26.6 (18.0-39.3). For the group with cardiac troponin, the reference category was negative troponin and negative CKMB; for the group with creatine kinase, the reference category was negative CKMB but either a positive or negative creatine kinase. CONCLUSION: Among the spectrum of ED patients with chest pain, an increased CKMB level with a normal creatine kinase level identifies patients at increased risk for acute coronary syndrome. Similarly, an increased troponin level regardless of CKMB level and an increased CKMB level regardless of troponin level identify patients at higher risk for acute coronary syndrome than those with uniformly normal cardiac biomarker levels. Our data suggest that discordant cardiac biomarkers may identify patients at increased risk for acute coronary syndrome.

Optimizing treatment and outcomes in acute heart failure: beyond initial triage.

Heart failure contributes substantially to health care costs in the United States due to its prevalence and frequent necessity for repeat hospitalizations to manage episodes of acute decompensation. Heart failure overwhelmingly impacts Medicare costs, as the highest proportion of heart failure patients are older than 65 years of age. Efforts to reduce morbidity, mortality, and health care resource utilization have been achieved successfully through emergency department-based heart failure observation units. For select patients, the observation unit can provide care with effective oral agents, including angiotensin-converting enzyme inhibitors, beta-adrenergic receptor blockers, and diuretics, as well as administration of other vasoactive agents, followed by a discharge plan of effective heart failure education and rigorous follow-up management. As advanced pharmacologic and diagnostic therapies continue to emerge, the observation unit staff can play an integral role in the critical education and self-management tools that are needed by the patient to ultimately improve outcomes and quality of life.

Cardiac troponins in renal insufficiency: review and clinical implications.

Patients with renal insufficiency may have increased serum troponins even in the absence of clinically suspected acute myocardial ischemia. While cardiovascular disease is the most common cause of death in patients with renal failure, we are just beginning to understand the clinical meaning of serum troponin elevations. Serum troponin T is increased more frequently than troponin I in patients with renal failure, leading clinicians to question its specificity for the diagnosis of myocardial infarction. Many large-scale trials demonstrating the utility of serum troponins in predicting adverse events and in guiding therapy and intervention in acute coronary syndromes have excluded patients with renal failure. Despite persistent uncertainty about the mechanism of elevated serum troponins in patients with reduced renal function, data from smaller groups of renal failure patients have suggested that troponin elevations are associated with added risk, including an increase in mortality. It is possible that increases in serum troponin from baseline in patients with renal insufficiency admitted to hospital with acute coronary syndrome may signify myocardial necrosis. Further studies are needed to clarify this hypothesis.

Current and emerging issues with B-type natriuretic peptide. Roundtable discussion.

A brief panel discussion was held on March 23, 2005, in New York City following a live symposium for primary care physicians discussing the roles of B-type natriuretic peptide in a variety of cardiovascular diseases. The participants were Dr. Marc A. Silver, Advocate Christ Medical Center, Oak Lawn, IL; Dr. Clive Rosendorff, Mount Sinai School of Medicine, New York, NY and VA Medical Center, Bronx, NY; Dr. Robert Berkowitz, Hackensack University Medical Center, Hackensack, NJ; and Dr. W. Franklin Peacock IV, The Cleveland Clinic Department of Emergency Medicine, Cleveland, OH. Dr. Silver moderated the discussion. The panel gathered to review some of the questions that emerged from the symposium and the questions raised by the attendees. These are of interest and importance to all interested in heart failure and B-type natriuretic peptide.

Bench to bedside: electrophysiologic and clinical principles of noninvasive hemodynamic monitoring using impedance cardiography.

The evaluation of the hemodynamic state of the severely ill patient is a common problem in emergency medicine. While conventional vital signs offer some insight into delineating the circulatory pathophysiology, it is often impossible to determine the true clinical state from an analysis of blood pressure and heart rate alone. Cardiac output measurements by thermodilution have been the criterion standard for the evaluation of hemodynamics. However, this technology is invasive, expensive, time-consuming, and impractical for most emergency department environments. Impedance cardiography (ICG) is a noninvasive method of obtaining continuous measurements of hemodynamic data such as cardiac output that requires little technical expertise. ICG technology was first developed by NASA in the 1960s and is based on the idea that the human thorax is electrically a nonhomogeneous, bulk conductor. Variation in the impedance to flow of a high-frequency, low-magnitude alternating current across the thorax results in the generation of a measured waveform from which stroke volume can be calculated by a modification of the pulse contour method. To adequately judge the possible role of this technology in the practice of emergency medicine, it is important to have a sufficient understanding of the basic scientific principles involved as well as the clinical validity and limitations of the technique.

Risk stratification in women enrolled in the Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM).

OBJECTIVES: It has been reported that the mortality risk for heart failure differs between men and women. It has been postulated that this is due to differences in comorbid features. Variation in risk profiles by gender may limit the performance of stratification algorithms available for heart failure in women. This analysis examined the ability of a published risk stratification model to predict outcomes in women. METHODS: The Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM) database was used. Characteristics, treatments, and outcomes for men and women were compared. The ADHERE registry classification and regression tree (CART) analysis was used for the risk stratification evaluation. RESULTS: Of 10,984 ADHERE-EM patients, 5,736 (52.2%) were women. In-hospital mortality was similar between men and women (p = 0.727). Significant differences (p < 0.0002) were noted by gender in all three variables in the CART model (blood urea nitrogen [BUN] > or = 43 mg/dL, systolic blood pressure < 115 mm Hg, and serum creatinine > or = 2.75 mg/dL). However, the CART model effectively stratified both genders into distinct risk groups with no significant difference in mortality by gender within stratified groups. CONCLUSIONS: The ADHERE Registry CART tool is effective at predicting risk in ED patients, regardless of gender.

Illicit stimulant use in a United States heart failure population presenting to the emergency department (from the Acute Decompensated Heart Failure National Registry Emergency Module).

Illicit stimulant drug use may have a profound clinical impact in acute decompensated heart failure (ADHF). The chronic use of cocaine and methamphetamine may lead to overt cardiomyopathy and ADHF. The Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM) collected data on patients presenting to emergency departments with ADHF at 83 geographically dispersed hospitals in the United States. This registry was queried to determine the rate of self-reported illicit drug use in emergency department patients presenting with ADHF and compare these patients with those without illicit drug use. The registry enrolled 11,258 patients with ADHF with drug use data from January 2004 to March 2006. Of these patients, 594 (5.3%) self-reported current or past stimulant drug use. Compared with nonusers, these patients were more likely to be younger (median age 49.7 vs 76.1 years), to be African American (odds ratio 11.9, 95% confidence interval 9.8 to 14.4), and to have left ventricular ejection fractions <40% (odds ratio 3.4, 95% confidence interval 2.8 to 4.2). Admitted users had no difference in mortality (adjusted odds ratio 0.83, 95% confidence interval 0.25 to 2.72) compared with nonusers. In conclusion, data from ADHERE-EM suggest that a clinically important percentage of patients with ADHF report the use of illicit stimulant drugs. Although these patients are younger with a greater degree of LV dysfunction, they did not have greater risk-adjusted mortality.

ED patients with heart failure: identification of an observational unit-appropriate cohort.

OBJECTIVE: To identify factors that define a low-risk cohort of patients with acute decompensated heart failure who are suitable for management in an observation unit. METHODS: Prospective convenience sample of 538 patients who presented to an ED with a diagnosis of congestive heart failure. Observation unit appropriate was defined as a length of stay less than 24 hours and no adverse events (myocardial infarction, death, arrhythmia, or rehospitalization) during the 30-day follow-up period. RESULTS: Study criteria were met by 499 patients (mean age, 61 +/- 15 years), and 234 (47%) were women. Of these, 133 (27%) met the criteria for observation unit appropriateness. Independent predictors were systolic blood pressure of greater than 160 (odds ratio, 1.8; 95% confidence interval, 1.15-2.7) and normal troponin I (odds ratio, 14.7; 95% confidence interval, 1.9-105). CONCLUSION: Initial blood pressure and troponin I can help identify patients with congestive heart failure at low risk for prolonged hospitalization and adverse events and who are reasonable candidates for observation unit management.

Nesiritide added to standard care favorably reduces systolic blood pressure compared with standard care alone in patients with acute decompensated heart failure.

The Prospective Randomized Outcomes study of Acutely decompensated Congestive heart failure Treated Initially as Outpatients with Nesiritide (PROACTION) trial evaluated the safety of nesiritide administration in the emergency department in patients with decompensated heart failure. Patients (N=237) were treated for at least 12 hours with standard care plus either intravenous nesiritide or placebo. Compared to placebo, nesiritide favorably decreased systolic blood pressure (SBP) in patients with elevated baseline SBP, without negatively impacting patients with lower baseline SBP (SBP, >140 mm Hg: nesiritide, -28.7 mm Hg, vs placebo, -8.4 mm Hg [P<.001]; SBP, 101-140 mm Hg: nesiritide, -12.3 mm Hg, vs placebo, -5 mm Hg [P<.017]; SBP, <101 mm Hg: nesiritide, -1.2 mm Hg vs placebo, +16.7 mm Hg [P<.03]). Both treatment groups had similar incidences of symptomatic and asymptomatic hypotension. These data demonstrate that early administration of nesiritide in the emergency department is a safe and effective treatment of heart failure.

Emergency department management of patients with acute decompensated heart failure.

The Acute Decompensated HEart Failure National REgistry (ADHERE(R)) confirms that the management of decompensated heart failure is an emergency department (ED) problem, as more than 75% of patients admitted to the hospital with heart failure arrive through the ED. This emphasizes the need for collaboration among emergency medicine, cardiology, nephrology, and hospitalists in the management of acute decompensated heart failure. Such collaboration is important for several reasons, including the enhancement of patient care. It is also known that most hospitals lose money on heart failure admissions. Strategies that can be employed to limit hospital losses on heart failure include reducing admissions from the ED; decreasing the length of hospital stay; increasing the use of the observation unit; reducing re-admissions, particularly through the first 30 days; and reducing the use of high-resource areas such as the intensive care unit (ICU). This article will focus on initiatives that can be implemented in the ED to help with these strategies. In particular, we will discuss early initiation of therapy and its ability to improve length of stay, reduce re-admissions, and reduce ICU admissions. Use of the observation unit for the management of heart failure will also be discussed as a way of decreasing admissions from the ED.