On Jan 29, 1996 20:39:46, 'Harvey Louzon ' wrote: >Where I disagree is in the assertion that a single CK is of no >value in determining disposition. It can be if used properly..... > What about patients >who would otherwise be sent home based upon an unconvincing history and >non-diagnotic ECG? That is a subset of patients who may benefit from a >single enzyme determination. If the single CK (or fractionation) is >positive then the patient is admitted. Hedges JR; Rouan GW; Toltzis R; Goldstein-Wayne B; Stein Use of cardiac enzymes identifies patients with acute myocardial infarction otherwise unrecognized in the emergency department. Ann Emerg Med 1987 Mar;16(3):248-52 Recognition of an acute myocardial infarction in the patient with chest pain is a frequent challenge to the clinician. Previous studies suggest that cardiac enzymes are of limited value in identifying patients with acute MI in the emergency department. Such studies have not evaluated the use of cardiac enzyme tests to complement decision making in the population of patients clinically designated for ED release. We studied 773 ED visits by patients age greater than or equal to 30 years presenting with chest pain unexplained by thoracic trauma or radiographic abnormalities. Cardiac enzyme levels were not available to the clinicians at the time of the initial visit and disposition of these patients was determined solely by clinical and ECG evaluation. Of the 291 admitted patients, 46 had an MI; 22 of the MI patients had a normal creatine kinase (CK) level. Of the 482 patients released from the ED, 181 patients had an elevated CK level. Among the released patients were five patients with MI. Four released MI patients had a CK level greater than or equal to 200 IU/L and three had an elevated CK-MB fraction (greater than or equal to 12 IU/L). In the population of patients scheduled for release, an elevated CK-MB had sensitivity, specificity, and positive predictive value for MI of 60%, 100%, and 60%, respectively. Although cardiac enzymes cannot be used in isolation to make admission decisions, selective use of CK-MB for final screening of patients otherwise scheduled for ED release may enhance the initial admission of patients with MI at risk for unintentional release. (2) Braunwald et. al. Diagnosing and Managing Unstable Angina. Quick Reference Guide for CLinicians. No 10. AHCPR Publication no. 94-0603. I agree with Harvey on this one. The assertion that one CK-MB is of value has been an intermittantly controversial position to hold here in my residency. Frequently hearing that if one is sent then I must completely rule out the patient. I disagree, asserting that with proper documentation, one can easily avoid any legal ramifications. Quick logic goes as such: with an "accepted" missed MI rate of 3-4% and with the knowledge that roughly 1/2 - 2/3 of MI patients have an initial positive CK-MB, might we cut our missed MI rate by a half if we send an initial ED enzyme. I realize that these two populations may be different in that the missed MI group may not have as high an initial positive enzyme rate ( it may be higher ;-) . Fortunately, there is some science. In addition to the 1987 Annals article referenced by Harvey, there is a somewhat similar study by the same group in this months ( January, 1996 ) Academic EM journal on pages 7-14. Three of 67 (4%) MI patients initially slated for discarge were admitted based on positive ED enzyme levels, reducing their missed MI rate to 0%. I realize there are costs involved with this practice, likely we can fine tune the practice of sending enzymes on everyone. Perhaps the legal issue will have a turnaround : "Doctor, didn't you realize that sending one CK-MB may have reduced your missed MI rate and averted discharging the husband of the plaintiff....". Daniel M. Joyce, M.D. EM-3 Mt. Sinai Program, NYC There is no dispute that a three hour protocol (2) has better sensitivity than a single determination (88%). Or that a six hour protocol (3) has even better sensitivity (95%). A twelve to 24 hour statedgy (as in a chest pain unit) would serve to exclude nearly 100% of acute MIs. (2) Gibler et. al. Acute Myocardial Infarction in Chest Pain Patients With Nondiagnostic ECGs: Serial CK-MB Sampling in the Emergency Department. Ann Emer Med 1992;21:504-512 (3) Puleo et. al. Use of a Rapid Assay of Subforms of Creatine Kinase to Diagnose or Rule Out Acute Myocardial Infarction. NEJM 1994;331:561-6 --H. Louzon, M.D. Another issue is one of timing. Certainly I have no expectation that the CK will be elevated when the presentation is within 2 or 3 hours of onset (absent silent ischemia). The greater the time interval from the onset of chest pain to presentation in the ED, the more likely the CK is to be elevated. Beyond about ten hours this is certainly within (a heartbeat of) 100% (95% negative predictive value after 7 hours (3)). The sensitivity of this test and thus the weight afforded a negative result has to be interpreted in that context (1). Let me also observe that the great bulk of what has been written about enzyme diagnosis in acute MI is dead set against the idea of using spot samples to exclude it in the ED (2,3). Nevertheless, just as the *presenting* ECG has prognostic significance (4,5) so too does an initial normal CK determination (6,7). I realize that these were inpatient studies whose results cannot necessarily be extrapolated to justify outpatient management. Finally you asked what other people are doing in this regard. I won't try to speak for other people but results of a couple of surveys reveals that reliance upon spot CK is the rule in clinical practice rather than the exception, contrary to most recommendations (8,9). --H. Louzon MD (1) Lee TH, Weisberg MC, Cook EF, Daley K, Brand DA, Goldman L Evaluation of creatine kinase and creatine kinase-MB for diagnosing myocardial infarction. Clinical impact in the emergency room. Arch Intern Med 1987 Jan;147(1):115-21 We prospectively studied the performance of emergency room strategies using a single sampling of total creatine kinase (CK) only and total CK with, if total CK levels were elevated, CK-MB levels in 639 patients with acute chest pain, including 386 patients who were admitted and 253 patients who were discharged. Acute myocardial infarction was diagnosed in 104 patients and excluded in 535. An elevated total CK level had a sensitivity of only 38% and specificity of only 80%, whereas a CK-MB level over 5% of an elevated total CK level had a sensitivity of only 34% and specificity of 88%. The sensitivities of both CK and CK-MB were higher in patients who arrived more than four hours after the onset of symptoms, and, in this population, the strategy using CK-MB performed significantly better than the strategy using total CK alone. Since a very positive CK-MB in a low-risk patient can greatly raise the probability of myocardial infarction, future strategies using CK-MB may have a role in selected subsets in determining which patients should not be sent home. However, the sensitivity of a single sampling of CK and CK-MB is too low for these assays to be used to exclude myocardial infarction in the emergency room or to be used as the rationale for deciding not to admit a patient. (2) Bakker AJ, Koelemay MJ, Gorgels JP, van Vlies B, Smits R, Tijssen JG, Haagen FD Failure of new biochemical markers to exclude acute myocardial infarction at admission [see comments] Lancet 1993 Nov 13;342(8881):1220-2 In a substantial proportion of patients with suspected myocardial infarction, biochemical markers are needed for clinical decision-making at the time of admission, because electrocardiographic (ECG) recordings are inconclusive. We have assessed the usefulness for exclusion of myocardial infarction at admission of the newer markers creatine kinase MB (CK-MB) mass concentration, troponin T, and myoglobin in comparison with the routinely used markers creatine kinase (CK) and CK-MB activity. 290 consecutive patients were enrolled. Acute myocardial infarction was diagnosed on the basis of clinical history, ECG criteria, and time-dependent changes in CK and CK-MB activity. 153 patients had definite acute myocardial infarction. Troponin T had the highest sensitivity for prediction of acute myocardial infarction; high concentrations (above the upper reference limits) were found in 98 (64%) of the patients with infarctions compared with 92 (60%) for CK-MB mass concentration, 76 (50%) for myoglobin, 61 (40%) for CK activity, and 53 (35%) for CK-MB activity. However, troponin T also had the highest "false-positive" rate; of 137 patients without myocardial infarction, 36 (26%) had high troponin T concentrations. Sensitivity, specificity, and positive and negative predictive values were calculated in relation to time between onset of chest pain and hospital admission. Although CK-MB mass concentration was, by a small margin, the best marker in patients admitted within 8-10 h of onset of chest pain, all the markers had negative predictive values too low to allow exclusion of acute myocardial infarction at admission in patients with symptoms suggestive of myocardial infarction of less than 10 h duration. (3) de Winter RJ, Koster RW, Sturk A, Sanders GT Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room. Department of Cardiology, University of Amsterdam The Netherlands. Circulation 1995 Dec 15;92(12):3401-7 BACKGROUND: Ruling out acute myocardial infarction (AMI) on the basis of rapid assays for cardiac markers will allow early triage of patients and cost-effective use of available coronary care facilities. METHODS AND RESULTS: We studied the value of myoglobin, creatine kinase (CK)-MBmass, and troponin T in ruling out an AMI in the emergency room in 309 consecutive patients presenting with chest pain. The gold standard for AMI was the combination of history, ECG, and a typical curve of the CK-MB activity (CK-MBact). Myoglobin was the earliest marker, and its negative predictive value (NPV) was significantly higher than for CK-MBmass and troponin T from 3 to 6 hours after the onset of symptoms (myoglobin versus CK-MBmass, P < .03; myoglobin versus troponin T, P < .01). The NPV of myoglobin reached 89% 4 hours after the onset of symptoms. The NPV of CK-MBmass reached 95% 7 hours after the onset of symptoms. Troponin T was not an early marker for ruling out AMI, and NPV changed over time, together with CK-MBact. The early NPV was higher in a subgroup of patients with a low probability of the presence of AMI for the three markers. Cardiac markers rise earlier in patients with large infarcts than in patients with small infarcts as indicated by the cumulative proportion of the marker above the upper reference limit at each time point (myoglobin, P = .04; CK-MBmass, P = .013; troponin T, P = .016). CONCLUSIONS: For ruling out AMI in the emergency room, myoglobin is a better marker than CK-MBmass or troponin T from 3 until 6 hours after the onset of symptoms, but the maximal NPV reaches only 89%. At 7 hours, the NPV of CK-MBmass is 95%. The test characteristics are influenced by the probability of the presence of AMI in the patients studied and by the size of their AMI. Infarct size of AMI patients should be reported in studies evaluating cardiac markers. (4) Brush et. al. Use of the Initial Electrocardiogram to Predict In-Hospital COmplications of Acute Myocardial Infarction. NEJM 1985;312:1137-41 (5) Stark et. al. The Initial Electrocardiogram During Admission for Myocardial Infarction. Arch Int Med 1987;147:843-846 (6) Hedges JR, Young GP, Henkel GF, Gibler WB, Green TR, Swanson JR Early CK-MB elevations predict ischemic events in stable chest pain patients. Acad Emerg Med 1994 Jan-Feb;1(1):9-16 OBJECTIVE: To demonstrate that creatine kinase-MB fraction (CK-MB) elevations within three hours of presentation in the emergency department (ED) are associated with subsequent ischemic events in clinically stable chest pain patients. METHODS: Prospective cohort study at two university- affiliated teaching hospitals. Participants were consenting ED chest pain patients 25 years old or older without evidence of rhythm or hemodynamic instability (n = 449). Exclusions included ST-segment elevation > or = 0.1 mV in > or = 2 electrocardiogram leads, chest wall trauma, abnormal x-ray studies, and incomplete data collection. Measurements included presenting and three-hour CK-MB levels, presenting ECG, initial clinical impression of coronary care unit need, and clinical follow up. Monitored adverse events included myocardial ischemia necessitating coronary angioplasty or cardiac bypass surgery, recurrent in-hospital myocardial infarction, bradycardia requiring pacing, emergent cardioversion, cardiogenic shock, ventricular fibrillation, and death. RESULTS: Overall, nine (2%) of 449 patients experienced an ischemic event within the first 48 hours. All nine patients required either coronary angioplasty or bypass surgery. Four (44%) of the nine patients with 48-hour ischemic events had elevated CK-MB levels. Of 23 patients who had complications within one week of ED presentation, seven (30%) had elevated ED CK-MB levels. An elevated CK-MB level was associated with an ischemic event both within 48 hours (risk ratio 9.5; 95% CI 2.7-33.7) and within one week (risk ration 5.2; 95% CI 2.3-11.7). CONCLUSIONS: An elevated CK-MB level within three hours of ED presentation is associated with a subsequent ischemic event in the clinically stable chest pain patient without ST-segment elevation. However, the ED CK-MB identifies only a minority or otherwise low-risk patients who develop ischemic events; other markers for diagnosing myocardial ischemia in the ED are needed. (8) Tsang T, Neal C, Walker A, Taylor D, Sosnowski T, Poplawski S, Shragge D, Catellier D, Montague T, Teo K Patterns of practice in emergency department management of chest pain of suspected cardiac origin: clinical utility of single stat creatine kinase (CK) [see comments] J Emerg Med 1995 Jul-Aug;13(4):471-80 The patterns of practice and the clinical utility of a single stat creatine kinase (CK) level in the emergency department management of chest pain of suspected cardiac origin were examined by a prospective observational study using a two-part questionnaire, completed by physicians before and after availability of CK results. The results showed that of the 776 patients in the study, 135 were admitted to hospital with acute myocardial infarction (AMI), 285 were admitted for reasons other than AMI, 343 were discharged, and 13 died or were transferred to another hospital. Although initial and final diagnoses in the emergency department did not differ in 597 patients (77%), initial decisions to admit or discharge were made in only 244 (31%) patients without waiting for CK results, and in 401 (52%) cases, decisions on patient disposition were deferred. Of 218 patients who had elevated CK levels, 193 (89%) were admitted, 121 for AMI. Only five (< 1%) patients who would otherwise have been discharged were admitted because of elevated CK levels. Of the 343 discharges, 245 (71%) occurred after the physicians knew the CK results. It is concluded that emergency department physicians routinely make changes in their diagnostic and management decisions based on current information and as it becomes updated. This study also suggests that there appears to be a heavy reliance on a single CK assay, although the relative importance of this diagnostic test compared to other factors is not known. Further studies are necessary. (9) Saxena S, Anderson DW, Kaufman RL, Hannah JA, Wong ET Quality assurance study of cardiac isoenzyme utilization in a large teaching Arch Pathol Lab Med 1993 Feb;117(2):180-3 Guidelines for diagnosis of acute myocardial infarction recommend that, if acute myocardial infarction is suspected, creatine kinase (CK)-MB levels should be measured on admission and again at 12 and 24 hours. In light of these recommendations, we conducted a quality assurance study to determine whether utilization of CK-MB tests in our institution, a large, university-affiliated teaching hospital, was consistent with current guidelines. Also, several years ago, we had established a policy of cancelling lactate dehydrogenase isoenzyme orders if the request originated from an unauthorized location, unless it was approved by a laboratory staff. Since this policy led to a greater than 90% reduction in the requests for lactate dehydrogenase isoenzyme testing, an additional objective was to reevaluate this policy. Of 774 patients evaluated with CK-MB tests, 294 (38%) received only a single test. Of these single tests, 277 had normal results (CK-MB < 5%). For the remaining 17 patients, the single CK-MB test findings were abnormal (CK-MB > 5%) without follow-up testing. Only two CK-MB tests were ordered for 187 patients (24%). Three or more CK-MB tests were obtained in 293 cases (38%). When two or more CK-MB tests were ordered, the time interval between the first and second tests was inappropriately short in 70% and long in 24%. The recommended timing for the third CK-MB was followed in only 4% of cases. Review of 32 cancellations of lactate dehydrogenase isoenzyme tests disclosed that lactate dehydrogenase isoenzyme tests were requested when unnecessary in 26 cases. Despite published guidelines for use of CK-MB for acute myocardial infarction, physicians at our institution continue to use these tests inappropriately by ordering only single CK-MB tests or by ordering repetitions of CK-MB tests at excessively short or long intervals. ------------------------------------ And this was the thrust of Jerris Hedges' conclusion in that article that keeps coming up with respect to this topic.[1] In looking at 1042 (relatively) low risk patients, those >= 25 y with chest pain and no ST-segment elevation, a very small number (three of a total of 67 MI patients, or 4%) were detected soley on the basis of an elevated CK in the ED (two CK's were drawn, three hours apart). There were *no* known MI's missed in the ED. [1] Hedges, Jerris R, et al. Multicenter study of creatine kinase-MB use: effect on chest pain clinical decision making. Acad Emerg Med 1996; 3:7-15. ---------------------------------------- (2) Puleo et. al. Use of a Rapid Assay of Subforms of Creatine Kinase to Diagnose or Rule Out Acute Myocardial Infarction. NEJM 1994;331:561-6 ------------------ - "Standard cardiac enzyme levels were of almost no use as an emergency room indicator of myocardial infarction." [Lee TH, Cook EF, Weisberg M, et al. Acute chest pain in the emergency room. Identification and examination of low-risk patients. Arch Intern Med 1985; 145:65-9.] Abstract: ---------------------------------- N Engl J Med Vol. 324 no. 18 pp. 1239-46 DATE: 1991 May 2 Lee TH , Juarez G, Cook EF, Weisberg MC, Rouan GW, Brand DA, Goldman L Ruling out acute myocardial infarction. A prospective multicenter validation of a 12-hour strategy for patients at low risk Abstract BACKGROUND. Although previous investigations have suggested that 24 hours is required to exclude acute myocardial infarction in patients who are admitted to a coronary care unit for the evaluation of acute chest pain, we hypothesized that a 12-hour period might be adequate for patients with a low probability of infarction at the time of admission. METHODS. Using a Bayesian model, we developed a strategy to identify candidates for a shorter period of observation from an analysis of a derivation set of 976 patients with acute chest pain who were admitted to three teaching and four community hospitals. In the derivation set, patients whose clinical characteristics in the emergency room predicted a low (less than or equal to 7 percent) probability of myocardial infarction had only a 0.4 percent risk of infarction if they had neither abnormal levels of cardiac enzymes nor recurrent ischemic pain during the first 12 hours of hospitalization. In an independent testing set of 2684 patients from the seven hospitals, 957 admitted patients (36 percent) were classified as candidates for this 12-hour period of observation according to a previously published multivariate algorithm. Few of these patients were actually transferred from a monitored setting at 12 hours. RESULTS. Of the 771 candidates for a 12-hour period of observation who did not have enzyme abnormalities or recurrent pain during the first 12 hours, 4 (0.5 percent) were subsequently found to have acute myocardial infarction, and only 3 (0.4 percent) died after primary cardiac arrests, all of which occurred three to five days after admission. Rates of other major cardiovascular complications were low in the patients who might have been transferred from the coronary care unit after 12 hours with this strategy. In patients with a higher initial risk of infarction, the standard strategy of 24-hour observation identified all but 11 of 739 acute myocardial infarctions (1 percent). CONCLUSIONS. Emergency room clinical data can be used to identify a large subgroup of patients for whom a 12-hour period of observation is normally sufficient to exclude acute myocardial infarction. Patient-specific evaluation and treatment can then proceed without the restrictions imposed by "rule-out" protocols for myocardial infarction.