Prognostic Value of Sensitive Troponin T in Patients with Stable and Unstable Angina and Undetectable Conventional Troponin

The Journal of Emergency Medicine, Vol. 40, No. 6, pp. 720–724, 2011 Copyright Ó 2011 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

Abstracts , CLINICAL COURSE OF REPEATED SUPRATHERAPEUTIC INGESTION OF ACETAMINOPHEN. Alhelail MA, Hoppe JA, Rhyee SH, Heard KJ. Clin Toxicol (Phila) 2011:49;108–12. This secondary analysis of a multicenter retrospective chart review was designed to describe the clinical course of patients treated for repeated supratherapeutic ingestions (RSTI) of acetaminophen with either intravenous (i.v.), or oral N-acetylcysteine (NAC). One hundred nineteen patients were identified from established registries at the participating institutions as having RSTI of acetaminophen, defined as ingestions of > 4 g of acetaminophen in 24 h over a period of 8 h or more. All patients were treated with either intravenous or oral NAC. Of the patients with identified RSTI, 63 (52.9%) were treated with i.v. NAC, and 56 (47.1%) with oral NAC; 93.3% survived, 3.4% died, and 1.7% (2 patients) received a liver transplant. The authors found that of the 115 patients with alanine aminotransferase (ALT) available at admission, 28.7% presented with hepatotoxicity (ALT > 1000), 7% presented with an ALT < 1000 IU/L and went on to develop hepatotoxicity, and 64.3% never developed an ALT > 1000 IU/L. Of the patients who went on to develop hepatotoxicity, the lowest ALT level on presentation was 252 IU/L, and among the patients who went on to die, or receive transplants, the lowest ALT on presentation was 426 IU/L. Risk factors associated with increased risk for death or transplantation identified among the patients include a history of alcoholism, viral hepatitis, liver disease, international normalized ratio above 1.5, and creatinine above 1.3 mg/dL. The authors concluded that the risk of RSTI-induced hepatotoxicity and poor outcomes may be predicted upon presentation. [Ann Arens, MD Denver Health Medical Center, Denver, CO]

, PRE-HOSPITAL TRIAGE IN THE AMBULANCE REDUCES INFARCT SIZE AND IMPROVES CLINICAL OUTCOME. Postma S, Dambrink J-H, de Boer M-J, et al. Am Heart J 2011;161:276–82. This retrospective study evaluated the effect of pre-hospital triage (PHT) on patient clinical outcome (infarct size determined by peak elevation of cardiac enzymes, post-percutaneous coronary intervention [PCI] angiographic blood flow, and mortality) for patients identified with an ST-elevation myocardial infarction (STEMI) transported to PCI centers vs. other health facilities. Over 5000 patients with a diagnosis of STEMI that underwent PCI from 1998 to 2008 at the Isala Klinieken facility in the Netherlands were included in the study divided into two groups: 1) if able to diagnose STEMI by the pre-hospital contact, patients were triaged directly to the catherization laboratory (n = 2840, 55%) and 2) if unable to diagnosis STEMI in the pre-hospital setting, patients went to the closest hospital and were transferred to a PCI center once the diagnosis was established (n = 2288, 45%). Patients transferred directly to PCI centers were statistically closer to those centers than those who went to outlying hospitals and were later transferred; 28 km vs. 43 km, p < 0.001. Ischemic time for the PHT group was 184 min vs. 260 min in the transfer group. Of the clinical outcomes, TIMI (Thrombolysis in Myocardial Infarction) flow was better in the PHT group, as was 1-year mortality; 4.9% vs. 7.0%, p = 0.002. All of this benefit stemmed from improvement in mortality for those patients living the furthest away from PCI centers. The authors concluded that PHT is an effective way to reduce mortality in patients with STEMI. [Anna Engeln, MD Denver Health Medical Center, Denver, CO]

Comment: This retrospective study identified some elements predictive of poor outcome in patients with repeated supratherapeutic ingestions of acetaminophen. Although these identifying factors may assist with patient disposition and threshold to initiate treatment, a prospective study is needed to identify the ideal time to initiate treatment to prevent poor outcomes.

Comments: This study, though large, had significant methodologic flaws and limitations that put its conclusions into question. First and most importantly, this was a non-randomized, retrospective study. Second, the authors did not include 323 (5% of total) patients who were found to be false positives. Inclusion of these patients along with an analysis of any adverse events may have changed the findings. Finally, the authors reported a significant mortality benefit for the entire study cohort, but this is misleading as the entirety of the benefit was found in those patients living the furthest distance away. The benefit then, if there is one, and this would have to be proven in prospective trials, is really only for those patients living more than 20 miles from a PCI center. This is not a condition that exists in most urban centers and so the generalizability of these results is questionable.

, PROGNOSTIC VALUE OF SENSITIVE TROPONIN T IN PATIENTS WITH STABLE AND UNSTABLE ANGINA AND UNDETECTABLE CONVENTIONAL TROPONIN. Ndrepepa G, Braun S, Mehilli J, et al. Am Heart J 2011;161: 68–75. This German study evaluated the prognostic value of highly sensitive cardiac troponin assays in patients with stable and unstable angina presenting with undetectable levels by conventional 720

The Journal of Emergency Medicine troponin assay. Of the 1057 patients included in the study, 808 had stable angina and 249 had unstable angina. All of these patients had initial negative conventional troponin T assays, yet underwent some sort of coronary artery revascularization procedure in which both conventional and high-sensitivity troponin assays were drawn simultaneously on the same plasma sample immediately before the procedure. The total sensitive troponin T level (median [interquartile range]) was 0.008 ug/L. The authors subsequently followed 954 patients (of the 1057) for the next 4 years with annual telephone calls, with the primary outcome being mortality. Using multivariate linear regression, several variables were identified to be independently associated with an elevated sensitive troponin T, including elderly age, male gender, higher body mass index, presence of diabetes, unstable angina, increased New York Heart Association class, reduced left ventricular ejection fraction, elevated level of N-terminal pro-brain natriuretic peptide, reduced glomerular filtration rate, and elevated level of C-reactive protein. The authors also concluded that sensitive troponin T level was an independent predictor of 4-year mortality (adjusted hazard ratio = 1.47 with 95% confidence interval 1.17–1.84, p < 0.01 for each unit increase in the natural logarithm of the sensitive troponin T). [Nicole Seleno, MD Denver Health Medical Center, Denver, CO] Comments: Several important limitations to this study exist. First and foremost was the fact that only 63% of all deaths (52 patients) were of cardiovascular origin, putting some question on the authors’ conclusions. Additionally, sensitive troponin T did not predict the occurrence of non-fatal myocardial infarction, stroke, or the need for revascularization over the same period. It remains unclear whether or not highly sensitive troponin assays truly have a role in defining risk in this patient population. , TAMSULOSIN HYDROCHLORIDE VERSUS PLACEBO FOR MANAGEMENT OF DISTAL URETERAL STONES. Vincendeau S, Bellissant E, Houlgatte A, et al. Arch Intern Med 2010;170:2021–7. This randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of tamsulosin hydrochloride in emergency department patients presenting with a distal ureteral stone. One hundred twenty-nine patients found to have a radiopaque stone between 2 mm and 7 mm were randomized to receive either 0.4 mg tamsulosin (n = 66) or placebo (n = 63). All patients also received intravenous ketorolac and analgesia. Of those randomized, 7 were excluded for various reasons and 122 patients were included for analysis. The primary endpoint of the study was time to stone expulsion, and secondary endpoints included symptom relapse and the need for additional medications. The majority of patients spontaneously passed the stone by day 10 on average, with no statistical significance between the study groups (p = 0.82), and the number of patients not passing stones by day 42 showed no statistically significant difference between tamsulosin and placebo (p = 0.41). In addition, there was no statistical difference between the need for ureteroscopy or morphine between those receiving tamsulosin vs. placebo. [Anna Engeln, MD Denver Health Medical Center, Denver, CO]

721 Comments: This well-designed study demonstrated no benefit of tamsulosin as expulsive therapy for patients with small ureteral stones. This runs counter to the findings of some other studies that have demonstrated such a benefit. Clearly, larger, equally welldesigned trials may be needed to definitively answer the question. , INAPPROPRIATE ANTIBIOTIC THERAPY IN GRAM-NEGATIVE SEPSIS INCREASES HOSPITAL LENGTH OF STAY. Shorr AF, Micek ST, Welch EC, et al. Crit Care Med 2011;39:46–51. This retrospective cohort study was designed to identify the effect of inappropriate initial antibiotic therapy (IIAT) on hospital length of stay in patients with Gram-negative septic shock. Seven hundred sixty adult patients were included in the study. Subject candidates were identified as patients with severe sepsis based on American College of Chest Physicians/Society of Critical Care Medicine consensus definition, and had evidence of a Gram-negative pathogen identified on culture, including: blood cultures, sputum and lower airway cultures, urine cultures, intraabdominal cultures, and central venous catheter cultures. Patients were included in analysis if they had persistent bacteremia defined as positive blood cultures drawn more than 5 days after the first set. IIAT included patients that did not receive an antimicrobial agent effective against the identified organism(s) in vitro, or if antimicrobials were not initiated within 24 h of drawing the positive blood cultures. Day 0 for length of stay was designated as the day cultures were obtained. The authors found that of the one-third (31.3%) of patients with IIAT, delay of therapy was responsible for the majority of the cases (58%). The most common pathogen identified was Escherichia coli (n = 225), with urinary tract infections the most common site of primary infection (51.1%). Patients with IIATwere more likely to have been admitted from a nursing home, be on chronic dialysis, and have underlying cancer or diabetes. Patients identified with IIAT had an independently increased length of stay by 2 days. Patients with IIAT also showed increased rates of in-hospital mortality compared with patients treated appropriately (51.7% vs. 36.4%, respectively). The authors concluded that IIAT is associated with increased length of stay, and in-hospital mortality. [Ann Arens, MD Denver Health Medical Center, Denver, CO] Comment: The timely initiation of appropriate antibiotics is known to make an impact on patient outcomes in sepsis, and this study found that delay to antibiotic therapy accounted for the majority of inappropriate antibiotic therapy cases. As a retrospective study, it is impossible to come to an understanding as to what led to the delays in therapy. Nonetheless, it remains important to remember that early initiation of appropriate antibiotics in the emergency department can improve morbidity and mortality in patients with Gram-negative sepsis. , CT-BASED BALLISTIC WOUND PATH IDENTIFICATION AND TRAJECTORYANALYSIS IN ANATOMIC BALLISTIC PHANTOMS. Folio LR, Fischer TV, Shogan PJ, et al. Radiology 2011;258:923–9. The purpose of this small pilot study was to determine the accuracy of computed tomography (CT)-based ballistic wound