e THE INFLUENCE OF EARLY HEMODYNAMIC OP-TIMIZATION ON BIOMARKER PATTERNS OF SE-VERE SEPSIS AND SEPTIC SHOCK. Rivers EP, Kruse JA,Jacobsen G, et al. Crit Care Med 2007;35:2016–24.

This study of 243 patients presenting with severe sepsis andseptic shock to an urban Emergency Department in the UnitedStates randomized patients to receive standard or early goal-directed treatment (EGDT) for sepsis. Biomarker patterns werecompared between the two initial treatment groups, and againafter patients were combined and stratified into three groupsbased on severity of global tissue hypoxia as evidenced bylactate level and central venous oxyhemoglobin saturation. Thestudy goal was to determine whether there are significantassociations between biomarker levels and resuscitation strat-egy, severity of global hypoxia, severity of organ dysfunction,and mortality of patients during early severe sepsis and septicshock. Biological samples, clinical findings, and laboratorydata were collected at 0, 3, 6, 12, 24, 48, 60, and 72 h frompresentation, and patients were followed until hospital dis-charge. The biomarkers assessed are pro-inflammatory, anti-inflammatory, endothelial, and apoptotic markers of the sys-temic inflammatory response, which include: interleukin-1receptor antagonist (IL-1ra), intercellular adhesion molecule-1(ICAM-1), tumor necrosis factor alpha (TNF-alpha), caspase-3,and interleukin-8 (IL-8). There were no statistically significantdifferences between groups in hour-0 demographics, clinicalmarkers, antibiotic treatment, baseline organ dysfunction, orbiomarker concentrations. EGDT resulted in significantly lowerpeak biomarker concentrations, and lower biomarker levels inthe first 72 h after presentation with divergent patterns betweentreatment groups appearing as early as the 3-h mark. There wasalso a significant correlation between biomarker levels anddegree of global tissue hypoxia, organ dysfunction scores, andearly mortality. The authors conclude that divergent biomarkerpatterns develop within 3 h of hospital presentation in responseto differing early treatment strategies. This association suggeststhat global tissue hypoxia is an important contributor to theearly inflammatory response. As higher biomarker levels cor-relate with poorer outcomes, the findings support early hemo-dynamic optimization in the management of adults with severesepsis and septic shock.

[Emily Johnston, MD,

Denver Health Medical Center, Denver, CO]

Editor’s Comment: EGDT has previously been shown tosignificantly reduce mortality in patients presenting with sepsisto the Emergency Department. This study demonstrateschanges in many biomarkers related to inflammation and tissueinjury that indicate a biological basis for EGDT’s beneficialeffects on outcome. These changes occur within 3 h of theinitiation of treatment and again reinforce the importance ofthis treatment strategy for appropriate patients.

e STRESS ECHOCARDIOGRAPHY, STRESS SINGLE-PHOTON-EMISSION COMPUTED TOMOGRAPHYAND ELECTRON BEAM COMPUTED TOMOGRAPHYFOR THE ASSESSMENT OF CORONARY ARTERY

DISEASE: A META-ANALYSIS OF DIAGNOSTIC PER-FORMANCE. Heijenbrok-Kal MH, Fleischmann KE, HuninkMG. Am Heart J 2007;154:415–23.

This study combined previous meta-analyses that investi-gated the diagnostic performance of imaging tests for coronaryartery disease (CAD). In each, the sensitivities, specificities,and diagnostic odds ratios were calculated by imaging modal-ity. In addition, a random effects summary receiver operatingcharacteristic analysis was performed as a means to compen-sate for the differences between each of the primary studies.The authors analyzed 11 meta-analyses that included 351 pa-tient series. Each modality was compared to the gold standardof coronary artery angiography in its ability to demonstrateCAD, defined as 50–100% stenosis in at least one coronaryartery. This study found the sensitivity of electron beam com-puted tomography (EBCT) to be the highest (93.1%), followedby stress single-photon-emission computed tomography(SPECT) at 88.1%, and stress echocardiography (79%). Stressechocardiography had the highest specificity (87.1%), followedby stress SPECT (73.0%) and EBCT (54.5%). The diagnosticodds ratio for each modality was calculated, taking into accountboth sensitivity and specificity, and showed no significant dif-ference between the three modalities. The authors conclude thatthere are no significant differences in the overall diagnosticperformance of stress echocardiography, stress SPECT, andEBCT when evaluating patients for CAD, but that each mo-dality may be more or less useful in particular patient settingswhen taking into account the sensitivity and specificity of eachmodality.

[Elijah Edwards, MD,

Denver Health Medical Center, Denver, CO]

Comment: It is important for emergency physicians to un-derstand the utility of non-invasive modalities available todiagnose CAD. Although coronary angiography continues to bethe gold standard for diagnosis of CAD, non-invasive modal-ities can be effective and this study concludes that there is nodifference in the overall performance of three such modalitiesin diagnosing CAD.

e DOES COMPRESSION-ONLY CARDIOPULMO-NARY RESUSCITATION GENERATE ADEQUATEPASSIVE VENTILATION DURING CARDIAC AR-REST? Deakin CD, O’Neill JF, Tabor T. Resuscitation 2007;75:53–9.

This study from the United Kingdom examined 17 patientsaged 18 years and older with in- or out-of-hospital cardiacarrest over a 12-month period to determine if compression-onlycardiopulmonary resuscitation (CPR) provided adequate pas-sive ventilation. All patients with cardiac arrest were initiallygiven manual chest compressions and then switched to me-chanical chest compressions, using a LUCAS device. All pa-tients were intubated and ventilated with 100% oxygen. Ven-tilatory pauses of approximately 1 min during central lineplacement provided the opportunity to collect respiratory datawhile the patients were apneic. Passive ventilation from me-chanical ventilation provided a median inspiratory volume per

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compression of 41.5 mL, a median minute volume carbondioxide (CO2) of 19.5 mL, a median end-tidal CO2 of 0.93kilopascals, and a median anatomical dead space of 162.7 mL.The authors concluded that passive ventilation during compres-sion-only CPR does not provide adequate gas exchange, how-ever, the majority of patients in the study were 40–50 minpost-arrest at the time of respiratory data collection, makingpulmonary edema and venous congestion limiting factors forgas exchange.

[Jessica Brooks, MD,

Denver Health Medical Center, Denver, CO]

Comment: This study was limited by many factors; the40–50 min arrest time before collection of data, the smallsample size, the use of compression-only CPR for only 1 min,and the use of only physiological outcomes instead of clinicaloutcomes. However, it does indicate that in the EmergencyDepartment, we should not be using compression-only CPR asit does not provide adequate gas exchange for ventilation. Morestudies are necessary to fully examine the concept of compres-sion-only CPR.

e TIMING OF ISCHEMIC ONSET ESTIMATEDFROM THE ELECTROCARDIOGRAM IS BETTERTHAN HISTORICAL TIMING FOR PREDICTINGOUTCOME AFTER REPERFUSION THERAPY FORACUTE ANTERIOR MYOCARDIAL INFARCTION: ADANISH TRIAL IN ACUTE MYOCARDIAL INFARC-TION 2 (DANAMI-2) SUBSTUDY. Sejersten M, Ripa RS,Maynard C, et al. Am Heart J 2007;154:61.e1–8.

This multi-center study compared the use of an electrocar-diographic acuteness score (Anderson-Wilkins acuteness score)

to patient history (historical timing) for predicting myocardialsalvage and prognosis in patients with acute anterior myocar-dial infarctions (AMIs) when treated with fibrinolysis or pri-mary percutaneous coronary intervention. One hundred seven-ty-five patients with anterior AMIs without electrocardiogram(ECG) confounding factors were included in the study. TheAnderson-Wilkins (AW) acuteness score was calculated foreach admission ECG for all included patients as the method forestimating timing of AMI. Historical timing was determinedfrom time of symptom onset to initiation of reperfusion ther-apy. Outcome data were determined from two standard restingECGs, a randomized ECG, and a follow-up ECG at predis-charge or at 1-month follow-up. From these ECGs, myocardialsalvage and infarct size were determined using both the Aldrichscore and the Selvester score. The authors found an associationbetween AW acuteness score and myocardial salvage (p �0.0001), whereas myocardial salvage was independent of his-torical timing (p � 0.9). The authors conclude that the ECGmethod of timing was superior to historical timing in predictingmyocardial salvage and prognosis after reperfusion therapy andsuggest that ECG estimation of the duration of ischemia mightprovide a more objective means to select patients for acutereperfusion therapy.

[Brad Talley, MD,

Denver Health Medical Center, Denver, CO]

Comment: This study suggests that using an objective vari-able such as an electrocardiogram acuteness score may bebetter in predicting the benefit of reperfusion therapy in certainpatients and thereby potentially change the proportion of AMIpatients eligible for reperfusion therapy. However, the AWacuteness score is time-consuming to calculate by hand andmay not be an appropriate tool for use in the EmergencyDepartment.

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