correlation coefficient of 0.22, 95% confidence interval [CI]0.20–0.24; p � 0.001) and individual study centers (interclasscorrelation coefficient of 0.66, 95% CI 0.62–0.70; p � 0.001).Patients treated with AEDs had significantly higher odds ofhaving an unfavorable outcome relative to those without AEDuse based on Glasgow Outcome Scale score after adjustmentfor study center, neurological grade, age, and systolic bloodpressure on admission (odds ratio [OR] 1.56, 95% CI 1.16–2.10; p � 0.003). The odds ratios of all in-hospital complica-tions were higher in patients treated with AEDs compared tothose without AED use, and included cerebral vasospasm (OR1.87, 95% CI 1.43–2.44; p � 0.001), neurological deterioration(OR 1.61, 95% CI 1.25–2.06; p � 0.001), cerebral infarction(OR 1.33, 95% CI 1.01–1.74; p � 0.04), and elevated temper-atures (OR 1.36, 95% CI 1.03–1.80; p � 0.03). The authorsconclude that prophylactic AED treatment in patients withSAH is common, follows an arbitrary prescribing pattern basedon institution and physician, and may be associated with in-creased in-hospital complications and possible worse outcome.

[Brad Talley, MD,

Denver Health Medical Center, Denver, CO]

Comment: The use of antiepileptic drugs is common yetarbitrary, varying by institution and individual neurosurgeonpreference. Given the lack of evidence of benefit from AEDand the possible adverse effects of the drugs, the use of pro-phylactic AEDs for SAH should be reconsidered and not rou-tinely started in the Emergency Department.

e UNDERSTANDING THE INFLAMMATORY CYTO-KINE RESPONSE IN PNEUMONIA AND SEPSIS. KellumJA, Lan K, Fink MP, et al. Arch Intern Med 2007;167:1655–63.

This multi-center cohort study examined 1886 patients ad-mitted to hospitals for pneumonia to determine whether specificcytokine patterns are associated with severe sepsis and death.All patients enrolled in the study had clinical and radiologicalevidence of pneumonia. Blood was drawn for cytokine assaysupon admission, then daily for the first week, then weeklywhile patients remained in the hospital. Cytokines examinedincluded tumor necrosis factor (TNF), interleukin 6 (IL-6)(pro-inflammatory), and interleukin 10 (IL-10) (anti-inflamma-tory.) The authors looked at the differences in cytokine levelsbetween patients who never developed severe sepsis, those whodeveloped severe sepsis and survived, and those who developedsevere sepsis and died. On day 1 of the study, mean cytokineconcentrations were elevated. However, normal concentrationsof IL-6, TNF, and IL-10 were seen in 17%, 64%, and 63% ofpatients, respectively. There were significant differences in thelevels of all three cytokines between the three groups of pa-tients. The mean cytokine levels of IL-6, TNF, and IL-10 weregreater on day 1 in patients with severe sepsis when comparedto patients who did not have severe sepsis (p value � 0.001 forall cytokines). Similarly, in those patients who did not havesevere sepsis on day 1 but later developed severe sepsis, meancytokine levels were higher than in those who never developedsevere sepsis (p value � 0.001 for all cytokines). In those

patients who did develop severe sepsis, mean cytokine levelswere higher in those who died than in those who survived (pvalue 0.01 for IL-6, 0.01 for IL-12, and 0.22 for TNF). How-ever, 4 of 149 cases of severe sepsis had no cytokine elevation,and some patients who never developed severe sepsis hadcytokine elevation. Cytokine levels remained elevated longerthan clinical signs of illness, with � 50% of patients havingtwo criteria for the systemic inflammatory response syndromeby day 2, despite more than 50% of patients still havingelevated IL-6 levels on day 7. Although systemic cytokinelevels were higher in patients with poorer outcomes, the dif-ference between groups of patients was not dramatic. Further-more, many patients with elevated cytokine levels had goodoutcomes, suggesting that cytokine activation is not necessarilyharmful. Interestingly, cytokine activation persisted muchlonger than the standard course of anti-cytokine treatmentsused in previous trials. The authors concluded that the cytokineresponse to infection and severe sepsis is longer in duration andmore variable than described in previous studies, however,there is a significant pattern of increased risk of severe sepsisand death in patients with markedly elevated cytokine levels.

[Jessica Brooks, MD,

Denver Health Medical Center, Denver, CO]

Editor’s Comment: This study reinforces the concept thatunderstanding the magnitude of the complicated inflammatorycascade seen in sepsis is not amenable to measurement of anyone specific marker. Although both inflammatory and anti-inflammatory cytokine activation seems to play a role in infec-tion and sepsis, the exact significance of their absolute levelsremains unclear. This study is limited by the very specific entrycriteria and thus cannot necessarily be generalized to all pa-tients with sepsis or infection. Further studies of patients withsepsis may bring to light more information regarding the utilityof measuring cytokine levels or using cytokine-based therapies.Until then, routine measurement of cytokine levels in the Emer-gency Department does not seem to be useful.

e ENOXAPARIN DOSING AND ASSOCIATED RISKOF IN-HOSPITAL BLEEDING AND DEATH IN PA-TIENTS WITH NON-ST SEGMENT ELEVATIONACUTE CORONARY SYNDROMES. LaPointe NM, ChenAY, Alexander KP, et al. Arch Intern Med 2007;167:1539–44.

This study sought to determine the extent that enoxaparin isdosed at current recommendations for non-ST elevation acutecoronary syndrome (ACS). A patient cohort that received enox-aparin for non-ST elevation ACS was obtained using a data setfrom the CRUSADE (Can Rapid Risk Stratification of UnstableAngina Patient Suppress Adverse Outcomes with Early Imple-mentation of the American College of Cardiology/AmericanHeart Association Guidelines) National Quality ImprovementInitiative. The authors also evaluated the outcomes in thosepatients who received excess dosing of enoxaparin (� 10 mgabove recommended daily dose) and lower-than-recommendedenoxaparin dosing (� 10 mg below recommended daily dose).Of 10,687 patients who received enoxaparin, 2002 (18.7%)received an excessive dose and 3116 (29.2%) received a lower-

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than-recommend dose. The patients who received excessivedosing of enoxaparin were older (median age 78 vs. 66 years,respectively), smaller (median body mass index 26.2 vs. 27.8,respectively), and more likely to be female (59.5% vs. 38.2%,respectively) than patients who received the recommendeddoses of enoxaparin (p � 0.001). Excessive dosing of enox-aparin was associated with a higher incidence of major bleed-ing (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.18–1.75) and death (OR 1.35; 95% CI 1.02–1.77) compared topatients receiving recommended doses of enoxaparin. Lower-than-recommended dosing of enoxaparin was associated with atrend toward increased mortality (OR 1.25; 95% CI 0.93–1.68).The authors conclude that although enoxaparin is an effectivedrug in the treatment of non-ST elevation ACS, nearly 1 in 5patients received excessive enoxaparin dosing, and that thiswas independently associated with an increased risk of majorbleeding and death.

[Elijah Edwards, MD,

Denver Health Medical Center, Denver, CO]

Editor’s Comment: Enoxaparin is recommended for use inpatients with non-ST elevation ACS but may be associated withsignificant problems if overdosed. Patient risk factors for over-dosing, such as older age, lower weight, and female gender,should be considered in the Emergency Department and takeninto account before the dosing and administration of enoxapa-rin.

e OUTCOME FROM PEDIATRIC CARDIAC ARRESTASSOCIATED WITH TRAUMA. Crewdson K, Lockey D,Davies G. Resuscitation 2007;75:29–34.

This study from the United Kingdom is a retrospectivereview of pediatric trauma patients requiring cardiopulmonaryresuscitation (CPR) in the pre-hospital setting, examining sur-vival rates of those patients, and identifying characteristics thatmay be associated with survival. Eighty pediatric trauma pa-tients, age 15 years or less, who received pre-hospital CPRwere identified from the London Helicopter Emergency Med-ical Service trauma database during a 10-year period (July 1994to June 2004). The London Helicopter Emergency MedicalService is a physician-led pre-hospital trauma service. CPR wasidentified by the use of high-dose adrenaline, external or inter-nal cardiac compressions, or defibrillation on scene or duringtransfer. Of the 80 children requiring pre-hospital CPR, 19(23.75%) survived to discharge from the Emergency Depart-ment, and 7 (8.75%) survived to be discharged from the hos-pital. Of the 7 survivors discharged from the hospital, 3 hadsustained hypoxic injuries, 2 had suffered asphyxial injuryassociated with blunt trauma, one had had a spinal cord injury,and the other had sustained a blunt injury in the setting of aknown congenital cardiac problem. There were no survivors ofpenetrating trauma. This study demonstrated improved but stillpoor outcomes as related in previous studies for pediatricpatients requiring pre-hospital CPR after trauma. The authorssuggest that outcomes may be better in physician-attended

pre-hospital resuscitations and that patients sustaining hypoxicor asphyxia injuries may do better than those sustaining hypo-volemic cardiac arrest.

[Brad Talley, MD,

Denver Health Medical Center, Denver, CO]

Editor’s Comment: This study confirms that cardiac arrestin pediatric trauma patients is rare and has poor outcomes.Children who sustain traumatic cardiac arrest precipitated byhypoxic or asphyxial insults may have the best chance ofsurviving with aggressive out-of-hospital resuscitation.

e SALINE OR ALBUMIN FOR FLUID RESUSCITA-TION IN PATIENTS WITH TRAUMATIC BRAIN IN-JURY. Myburgh J, Cooper JD, Finfer S, et al. N Engl J Med2007;357:874–84.

This study from New Zealand and Australia is a post hocanalysis of patient outcomes from the Saline vs. Albumin FluidEvaluation (SAFE) study. The SAFE trial was a double-blind,randomized, controlled trial comparing albumin and saline usein intensive care unit patients in 16 hospitals across Australiaand New Zealand over a 2 1/2 year period. In this study,investigators conducted a sub-group analysis of patients withtraumatic brain injury (TBI), analyzing outcomes based onmortality and functional neurological status at 24 months. In-terviews were conducted by trained assessors using a telephonequestionnaire to determine functional neurological outcomes.Criteria for traumatic brain injury were met if patients had ahistory of trauma, evidence of trauma on head computed to-mography scan, and Glasgow Coma Scale score � 13. Fourhundred sixty patients were followed, of whom 231 receivedalbumin and 229 received saline. The two groups were similarwith regards to physiologic and demographic parameters. At 24months, 33.2% of patients who received albumin had died,compared with 20.4% of patients who received saline (relativerisk 1.63, 95% confidence interval 1.17–2.26, p value 0.003.) Inpatients with severe head injury (Glasgow Coma Scale score3–8), the relative risk of death in patients who received albu-min was 1.88 (95% confidence interval 1.31–2.70). The authorsconcluded that the rate of death in TBI patients who receivedalbumin was significantly higher than in those who receivedsaline, particularly in patients with severe TBI, suggesting thatsaline is preferable to albumin in resuscitation of patients withTBI. The mechanism behind this difference is unclear, but maybe due to exacerbations of vasogenic or cytotoxic cerebraledema from albumin.

[Jessica Brooks, MD,

Denver Health Medical Center, Denver, CO]

Comment: Although it is a post hoc analysis, and thuspossessive of less power than a properly designed prospectivetrial, this study indicates that Emergency Physicians should beusing normal saline as opposed to albumin to resuscitate pa-tients with traumatic brain injury. It is another in a long line ofstudies that demonstrate similar results in a wide range ofdisease states. The diminishment of any role for the ED use ofalbumin continues with this information.

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