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Serum bicarbonate and anion gap cannot reliably predict elevated serum lactate levels
RESEARCH FORUM ABSTRACTS
not coupling causes the individual oscillators to eventually come into phase (ie, whether the population synchronizes). Previous studies have shown that populations of diffusively coupled identical oscillators tend to synchronize. Other studies have shown that populations of coupled oscillators with a range of natural frequencies may or may not synchronize, depending on the strength of coupling. Less is known about this question for populations of coupled stochastic (‘‘noisy’’) oscillators. A stochastic oscillator is characterized by random variation in the period and amplitude of oscillation. Because all biochemical systems are to some extent noisy, the behavior of such systems is relevant to biology. We examine under what conditions populations of diffusively coupled stochastic oscillators tend to synchronize. Methods: This was a theoretical study using computer simulation. Using an algorithm from the theory of stochastic dynamical systems, the behavior of populations of coupled stochastic oscillators was simulated. A model chemical oscillator known as the ‘‘Brusselator’’ was chosen for simulation. Each oscillator was coupled equally to all the others by a process akin to chemical diffusion. Two main sets of simulations were conducted. In the first, the strength of the coupling parameter was gradually increased from zero through 9 successive values to a maximum. All other system parameters were held constant. In the second set of simulations, the number of oscillators was set at 20, 30, 40, 50, 60, 70, 80, 90, and 100. All other system parameters were held constant, including strength of coupling. In each simulation, the average behavior of the population was graphed against time. For populations with no synchrony, the average behavior is expected to fluctuate irregularly around a baseline with no clear oscillatory behavior. For synchronized populations, the average is expected to clearly oscillate around a baseline. Results: As the coupling parameter is increased, there is a clear trend from no synchrony in the population to a high degree of synchrony. For higher values of the coupling parameter, the degree of synchrony increases less. As the number of oscillators in the population is increased, there is a clear trend from less synchrony to more synchrony. The degree of change in synchrony is less than that observed as the coupling parameter is varied. Conclusion: Increased coupling and increased population size tend to increase synchrony in populations of coupled stochastic oscillators. For the conditions examined, the effect of coupling is stronger than that of population size. Coupled biochemical oscillators may regularize and synchronize their behavior by stronger coupling or increased population size.
171
Albumin Cobalt Binding Test: A Gold Standard to Rule Out Acute Coronary Syndrome?
Abadie JM, Blassingane C, Bankson D/University of Washington Medical Center, Seattle, WA Study objectives: The purpose of this study is to validate the Albumin Cobalt Binding (ACB) test at the Veterans Affairs (VA) Puget Sound Health Care System. This study measures the distribution of ACB values for our normal VA population and determines an initial ACB rule-out value for acute coronary syndrome. Methods: ACB values were determined photometrically with Ischemia Technologies reagents on the P-module of a Roche Modular Analytical System. We retrospectively measured serum ACB levels in 21 first-draw troponin samples obtained from patients presenting to the emergency department with chest pain. Specifically, we chose these samples only if the patient’s initial troponin was negative and subsequent troponin levels became elevated. According to the correlations between the initial negative and subsequently elevated troponin, we constructed a receiver operating characteristic (ROC) curve to identify the highest ACB rule-out value. Furthermore, using 30 patients not experiencing chest pain, we established an initial normal range for our population. Results: There was a statistically significant difference between ACB values in the 30 apparently healthy individuals (85.5610.3 U/mL; 95% confidence interval [CI] 81.7 to 89.4) compared with the 21 patients whose troponin became positive (123.8617.2 U/mL; 95% CI 115.9 to 131.6; P\.0001). The area under the ROC curve was 99.1% (P\.0001), and there was almost complete discrimination between the 2 groups when a 96 U/mL decision level was used. Conclusion: This preliminary study suggests that the ACB test has a strong negative predictive value and sensitivity in the initial study group for predicting positive troponin results 6 to 24 hours after presentation. The ACB test, when used in conjunction with cardiac injury markers, holds promise in reducing inappropriate low-risk admissions.
S 5 4
172
Serum Bicarbonate and Anion Gap Cannot Reliably Predict Elevated Serum Lactate Levels
Spitalnic S, Sidman RD, Monti J/Rhode Island Hospital, Providence, RI Study objectives: New treatment strategies for severe sepsis and septic shock have made it important to rapidly identify patients with serum lactate levels greater than 4.0 mmol/L. The measurement of serum electrolyte levels is generally considered routine for patients with significant medical illness; the measurement of lactate levels is not as universal. We ask how well a reduced serum bicarbonate level (\20 mmol/L) or an elevated anion gap (Na1K-CO3-Cl[20) predict a lactate level of 4.0 mmol/L or greater. Methods: This was a retrospective medical record review at a university hospital. Laboratory results were reviewed for patients 18 years of age or older who, during a 2-month period, had time-matched determinations of serum lactate and electrolyte levels. The correlation of lactate with both bicarbonate and anion gap was determined, and the test properties of each as a screening test for a lactate greater than 4.0 mmol/L were determined. Results: One hundred twenty-five patients (58% female patients, age range 2 months to 97 years) had lactate and electrolyte levels measured concurrently during the study period. Lactate level was greater than 4.0 mmol/L in 17% of patients. The sensitivity and specificity of a reduced bicarbonate were 38% (95% confidence interval [CI] 18% to 62%) and 78% (95% CI 69% to 85%), respectively. The sensitivity and specificity of an elevated anion gap were 38% (95% CI 18% to 62%) and 89% (95% CI 82% to 95%), respectively. There was only minimal correlation between bicarbonate or anion gap and lactate level (r=0.06 and 0.11, respectively). Conclusion: A lactate level greater than 4.0 mmol/L cannot be predicted from either reduced bicarbonate or an elevated anion gap. Measuring bicarbonate or calculating the anion gap cannot be considered appropriate screens when attempting to identify patients who may benefit from aggressive sepsis management.
173
The Anion Gap Is Not a Reliable Screening Test for Lactic Acidosis in Emergency Department Patients
Bonzani TA, Adams BA/San Antonio Uniformed Services University of Health Sciences, San Antonio, TX Study objectives: Lactic acidosis portends a poor prognosis in trauma, sepsis, and other shock states and is useful for triaging and resuscitating emergency department (ED) patients. The anion gap is commonly taught to be a good predictor of lactic acidosis. However, some ICU studies show that the anion gap may be insensitive to lactic acidosis. We seek to determine whether the anion gap is a sensitive predictor of lactic acidosis in the ED setting. Methods: This was a retrospective cohort design using a laboratory database and explicit medical record review in a military academic ED with a 50,000 annual census. Participants were all ED patients over a 7-month period who had lactic acidosis level drawn for clinical indications. Patients were excluded if the anion gap and lactic acidosis values were drawn more than 60 minutes apart or for presence of ketoacidosis or an anion gap–inducing toxic ingestion. Baseline demographic data, hospital mortality, admission, and discharge diagnoses were the outcome measures. Venous or arterial lactic acidosis specimens were analyzed on a Vitros 950 using colorimetric methodology (normal up to 2.5 mmol/L). The anion gap was calculated by [Na–Cl–CO2] on the Vitros 950 using potentiometric methodology. Sensitivity analyses with 95% confidence intervals (CIs) of the anion gap for detecting presence of lactic acidosis were calculated for the traditional anion gap normal value (anion gap present if [12.0) and for the lower anion gap normal value when using newer ion-selective electrode assay (anion gap present if [6.0). Results: We performed an interim data analysis of 207 patients, of whom 61 were excluded by protocol. Of the 146 patients remaining, the average age was 66 years (range 16 to 94 years), and 48.6% of patients were women. There were 33 cases of lactic acidosis (22.6%) in this highly selected ED patient population. The most common diagnosis in the lactic acidosis cohort was severe sepsis. Hospital mortality was significantly higher in patients with lactic acidosis (24.2%) than in patients without lactic acidosis (2.6%; P\.0003). Using an anion gap cutoff of 12, the sensitivity is 45.4% (95% CI 28% to 63%) and specificity is 80.5% (95% CI 72% to 87%). Using an anion gap cutoff of 6, the sensitivity for lactic acidosis is 93.9% (95% CI 78% to 99%), with a specificity of 17.6% (95% CI 11% to 26%). Conclusion: Using the traditional definition of anion gap greater than 12, an electrolyte panel with calculated anion gap is poorly sensitive for presence of lactic acidosis. When using the newly revised anion gap of greater than 6 on ion-selective
ANNALS OF EMERGENCY MEDICINE
44:4
OCTOBER 2004
not coupling causes the individual oscillators to eventually come into phase (ie, whether the population synchronizes). Previous studies have shown that populations of diffusively coupled identical oscillators tend to synchronize. Other studies have shown that populations of coupled oscillators with a range of natural frequencies may or may not synchronize, depending on the strength of coupling. Less is known about this question for populations of coupled stochastic (‘‘noisy’’) oscillators. A stochastic oscillator is characterized by random variation in the period and amplitude of oscillation. Because all biochemical systems are to some extent noisy, the behavior of such systems is relevant to biology. We examine under what conditions populations of diffusively coupled stochastic oscillators tend to synchronize. Methods: This was a theoretical study using computer simulation. Using an algorithm from the theory of stochastic dynamical systems, the behavior of populations of coupled stochastic oscillators was simulated. A model chemical oscillator known as the ‘‘Brusselator’’ was chosen for simulation. Each oscillator was coupled equally to all the others by a process akin to chemical diffusion. Two main sets of simulations were conducted. In the first, the strength of the coupling parameter was gradually increased from zero through 9 successive values to a maximum. All other system parameters were held constant. In the second set of simulations, the number of oscillators was set at 20, 30, 40, 50, 60, 70, 80, 90, and 100. All other system parameters were held constant, including strength of coupling. In each simulation, the average behavior of the population was graphed against time. For populations with no synchrony, the average behavior is expected to fluctuate irregularly around a baseline with no clear oscillatory behavior. For synchronized populations, the average is expected to clearly oscillate around a baseline. Results: As the coupling parameter is increased, there is a clear trend from no synchrony in the population to a high degree of synchrony. For higher values of the coupling parameter, the degree of synchrony increases less. As the number of oscillators in the population is increased, there is a clear trend from less synchrony to more synchrony. The degree of change in synchrony is less than that observed as the coupling parameter is varied. Conclusion: Increased coupling and increased population size tend to increase synchrony in populations of coupled stochastic oscillators. For the conditions examined, the effect of coupling is stronger than that of population size. Coupled biochemical oscillators may regularize and synchronize their behavior by stronger coupling or increased population size.
171
Albumin Cobalt Binding Test: A Gold Standard to Rule Out Acute Coronary Syndrome?
Abadie JM, Blassingane C, Bankson D/University of Washington Medical Center, Seattle, WA Study objectives: The purpose of this study is to validate the Albumin Cobalt Binding (ACB) test at the Veterans Affairs (VA) Puget Sound Health Care System. This study measures the distribution of ACB values for our normal VA population and determines an initial ACB rule-out value for acute coronary syndrome. Methods: ACB values were determined photometrically with Ischemia Technologies reagents on the P-module of a Roche Modular Analytical System. We retrospectively measured serum ACB levels in 21 first-draw troponin samples obtained from patients presenting to the emergency department with chest pain. Specifically, we chose these samples only if the patient’s initial troponin was negative and subsequent troponin levels became elevated. According to the correlations between the initial negative and subsequently elevated troponin, we constructed a receiver operating characteristic (ROC) curve to identify the highest ACB rule-out value. Furthermore, using 30 patients not experiencing chest pain, we established an initial normal range for our population. Results: There was a statistically significant difference between ACB values in the 30 apparently healthy individuals (85.5610.3 U/mL; 95% confidence interval [CI] 81.7 to 89.4) compared with the 21 patients whose troponin became positive (123.8617.2 U/mL; 95% CI 115.9 to 131.6; P\.0001). The area under the ROC curve was 99.1% (P\.0001), and there was almost complete discrimination between the 2 groups when a 96 U/mL decision level was used. Conclusion: This preliminary study suggests that the ACB test has a strong negative predictive value and sensitivity in the initial study group for predicting positive troponin results 6 to 24 hours after presentation. The ACB test, when used in conjunction with cardiac injury markers, holds promise in reducing inappropriate low-risk admissions.
S 5 4
172
Serum Bicarbonate and Anion Gap Cannot Reliably Predict Elevated Serum Lactate Levels
Spitalnic S, Sidman RD, Monti J/Rhode Island Hospital, Providence, RI Study objectives: New treatment strategies for severe sepsis and septic shock have made it important to rapidly identify patients with serum lactate levels greater than 4.0 mmol/L. The measurement of serum electrolyte levels is generally considered routine for patients with significant medical illness; the measurement of lactate levels is not as universal. We ask how well a reduced serum bicarbonate level (\20 mmol/L) or an elevated anion gap (Na1K-CO3-Cl[20) predict a lactate level of 4.0 mmol/L or greater. Methods: This was a retrospective medical record review at a university hospital. Laboratory results were reviewed for patients 18 years of age or older who, during a 2-month period, had time-matched determinations of serum lactate and electrolyte levels. The correlation of lactate with both bicarbonate and anion gap was determined, and the test properties of each as a screening test for a lactate greater than 4.0 mmol/L were determined. Results: One hundred twenty-five patients (58% female patients, age range 2 months to 97 years) had lactate and electrolyte levels measured concurrently during the study period. Lactate level was greater than 4.0 mmol/L in 17% of patients. The sensitivity and specificity of a reduced bicarbonate were 38% (95% confidence interval [CI] 18% to 62%) and 78% (95% CI 69% to 85%), respectively. The sensitivity and specificity of an elevated anion gap were 38% (95% CI 18% to 62%) and 89% (95% CI 82% to 95%), respectively. There was only minimal correlation between bicarbonate or anion gap and lactate level (r=0.06 and 0.11, respectively). Conclusion: A lactate level greater than 4.0 mmol/L cannot be predicted from either reduced bicarbonate or an elevated anion gap. Measuring bicarbonate or calculating the anion gap cannot be considered appropriate screens when attempting to identify patients who may benefit from aggressive sepsis management.
173
The Anion Gap Is Not a Reliable Screening Test for Lactic Acidosis in Emergency Department Patients
Bonzani TA, Adams BA/San Antonio Uniformed Services University of Health Sciences, San Antonio, TX Study objectives: Lactic acidosis portends a poor prognosis in trauma, sepsis, and other shock states and is useful for triaging and resuscitating emergency department (ED) patients. The anion gap is commonly taught to be a good predictor of lactic acidosis. However, some ICU studies show that the anion gap may be insensitive to lactic acidosis. We seek to determine whether the anion gap is a sensitive predictor of lactic acidosis in the ED setting. Methods: This was a retrospective cohort design using a laboratory database and explicit medical record review in a military academic ED with a 50,000 annual census. Participants were all ED patients over a 7-month period who had lactic acidosis level drawn for clinical indications. Patients were excluded if the anion gap and lactic acidosis values were drawn more than 60 minutes apart or for presence of ketoacidosis or an anion gap–inducing toxic ingestion. Baseline demographic data, hospital mortality, admission, and discharge diagnoses were the outcome measures. Venous or arterial lactic acidosis specimens were analyzed on a Vitros 950 using colorimetric methodology (normal up to 2.5 mmol/L). The anion gap was calculated by [Na–Cl–CO2] on the Vitros 950 using potentiometric methodology. Sensitivity analyses with 95% confidence intervals (CIs) of the anion gap for detecting presence of lactic acidosis were calculated for the traditional anion gap normal value (anion gap present if [12.0) and for the lower anion gap normal value when using newer ion-selective electrode assay (anion gap present if [6.0). Results: We performed an interim data analysis of 207 patients, of whom 61 were excluded by protocol. Of the 146 patients remaining, the average age was 66 years (range 16 to 94 years), and 48.6% of patients were women. There were 33 cases of lactic acidosis (22.6%) in this highly selected ED patient population. The most common diagnosis in the lactic acidosis cohort was severe sepsis. Hospital mortality was significantly higher in patients with lactic acidosis (24.2%) than in patients without lactic acidosis (2.6%; P\.0003). Using an anion gap cutoff of 12, the sensitivity is 45.4% (95% CI 28% to 63%) and specificity is 80.5% (95% CI 72% to 87%). Using an anion gap cutoff of 6, the sensitivity for lactic acidosis is 93.9% (95% CI 78% to 99%), with a specificity of 17.6% (95% CI 11% to 26%). Conclusion: Using the traditional definition of anion gap greater than 12, an electrolyte panel with calculated anion gap is poorly sensitive for presence of lactic acidosis. When using the newly revised anion gap of greater than 6 on ion-selective
ANNALS OF EMERGENCY MEDICINE
44:4
OCTOBER 2004