BEYOND THE BLUE: What Fellows Are Reading in Other Journals Lung Cancer Screening, Targeted Temperature after Cardiac Arrest, and Vasopressin and Steroids in Cardiac Arrest Jennifer Y. Hwang, Anthony F. Arredondo, and Tessy K. Paul Department of Pulmonary and Critical Care Medicine, University of California, Los Angeles, Los Angeles, California Recommended Reading from the University of California, Los Angeles Fellows; Tisha Wang, M.D., Program Director

Aberle, et al.; National Lung Screening Trial Research Team. Results of the Two Incidence Screenings in the National Lung Screening Trial. N Engl J Med (1)

with CXR. However, this study illustrates the added sensitivity afforded by screening chest CT, with a trend toward earlier detection of lung cancer; albeit at the cost of specificity compared with CXR. n

Reviewed by Jennifer Y. Hwang


Lung cancer is the most common cause of cancer-related death in the United States. In 2002, the National Lung Screening Trial was created to investigate whether screening with low-dose computed tomography (CT), as compared with chest radiography (CXR), would reduce lung cancer–related mortality in asymptomatic, high-risk patients (age 55–74 yr, >30-pack-year smoking history, and cessation of cigarettes within the past 15 yr) (2). The results of the initial prevalence screen in 2011 showed a relative risk reduction in mortality of 20% with low-dose CT. This study reports findings from the first (T1) and second (T2) rounds of yearly incidence screening. At the T1 screen, positive results were found in 27.9% of patients in the CT group compared with 6.2% in the CXR group. The sensitivity for detection of lung cancer in CT versus CXR was 94.4 versus 59.6%, and the specificity was 72.6 versus 94.1%, respectively. During the T2 screen, 16.8% of patients in the CT group had positive results versus 5.0% of patients screened with CXR. The sensitivity for detection of lung cancer during T2 for CT compared with CXR was 93 versus 63.9%, with a specificity of 83.9 versus 95.3%, respectively. The authors postulated that the rates of positive screening overall decreased at T2 mainly because changes noted to be stable across all rounds could be categorized as negative results. Of the lung cancers detected, 31.1% were stage III or IV in the CT group versus 59.1% in the CXR group at T1. Stage distributions of cancer at T2 were similar to T1. The calculated incidence of stage IV lung cancer in CT screening was 138 per 100,000 person years versus 204 per 100,000 person years with CXR. Overall, this study showed that the proportion of positive screens with low-dose CT continued to remain significantly higher than CXR. CT screening also demonstrated a continued shift toward detection of earlier stage cancers at T1 and T2. The benefit to screening beyond 2 years remains unknown, and low-dose chest CT still provides considerable additional radiation exposure compared

1. Aberle DR, DeMello S, Berg CD, Black WC, Brewer B, Church TR, Clingan KL, Duan F, Fagerstrom RM, Gareen IF, et al.; National Lung Screening Trial Research Team. Results of the two incidence screenings in the National Lung Screening Trial. N Engl J Med 2013; 369:920–931. 2. Church TR, Black WC, Aberle DR, Berg CD, Clingan KL, Duan F, Fagerstrom RM, Gareen IF, Gierada DS, Jones GC, et al.; National Lung Screening Trial Research Team. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med 2013;368:1980–1991.

Nielsen, et al.; TTM Trial Investigators. Targeted Temperature Management at 338 C versus 368 C after Cardiac Arrest. N Engl J Med (3) Reviewed by Anthony F. Arredondo

Therapeutic hypothermia, generally defined as targeted temperature management with a goal temperature of 32–348 C, has been shown to improve both survival and neurologic function in two previous trials for unconscious patients in out-of-hospital cardiac arrests with shockable rhythms (4, 5). Based on these trials, international guidelines have extended the use of therapeutic hypothermia for cardiac arrest to those with nonshockable rhythms and in-hospital cardiac arrests (6). Debate has persisted regarding the generalizability of these guidelines and the true efficacy of therapeutic hypothermia. In one study (4), a greater incidence of fever in the control group, which portends worse outcomes, led some to conclude that the treatment effect was due to fever prevention rather than therapeutic hypothermia. In this multicenter international study, Nielsen and colleagues (3) randomized 950 subjects with unconscious, out-of-hospital

( Received in original form January 24, 2014; accepted in final form March 5, 2014 ) Correspondence and requests for reprints should be addressed to Tisha Wang, M.D., University of California, Los Angeles, Department of Pulmonary and Critical Care Medicine, Los Angeles, CA 90095. E-mail: [email protected] Am J Respir Crit Care Med Vol 189, Iss 8, pp 995–996, Apr 15, 2014 Copyright © 2014 by the American Thoracic Society DOI: 10.1164/rccm.201401-0133RR Internet address:

Beyond the Blue


BEYOND THE BLUE cardiac arrests to two treatment groups comparing target temperatures of 338 C versus 368 C regardless of initial rhythm. The primary outcome was all-cause mortality by the end of the trial, and the secondary outcome was poor neurologic function, as defined by Cerebral Performance Category (score 3–5) and modified Rankin scale (score 4–6) at 180 days. After 28 hours, rewarming was initiated for a total intervention time of 36 hours. Standard fever control continued for 72 hours after the cardiac arrest. At the end of the trial, 235 of 473 patients (50%) assigned to 338 C, and 225 of 466 patients (48%) assigned to 368 C had died (hazard ratio of the 338 C group = 1.06; 95% confidence interval = 0.89–1.28; P = 0.51), representing no significant difference in mortality between the groups. In addition, there was no statistical difference with respect to poor neurologic outcome at 180 days. Predefined subgroups, including those with shockable rhythms, revealed no difference in death or poor neurologic function between treatment groups. In summary, targeted temperature management at 338 C does not provide benefit to patients with out-of-hospital cardiac arrests when compared with 368 C. Although no harm was seen in the 338 C group, caution is advised for this target temperature given the lack of benefit for survival or adverse events. Limitations of this study include unblinding of the intensive care unit staff, lost data because of lack of legal consent, and absence of data regarding use of sedation and neuromuscular blockers. However, results from this study suggest that prevention of fever, rather than therapeutic cooling, may be the key factor and therapeutic goal in patients after cardiac arrest. n References 3. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al.; TTM Trial Investigators. Targeted temperature management at 338 C versus 368 C after cardiac arrest. N Engl J Med 2013;369:2197–2206. 4. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557–563. 5. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549–556. 6. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, et al.; American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010; 122(18 Suppl 3):S768–S786.

Mentzelopoulos, et al. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival after In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA (7) Reviewed by Tessy K. Paul

Survival and neurologic outcomes after in-hospital cardiac arrests remain dismal, with about half of surviving patients left with significant neurologic deficits. Data from a prior study demonstrated that adding vasopressin and corticosteroids to cardiopulmonary resuscitation (CPR) improved survival (8). In this study, 996

Mentzelopoulos and colleagues (7) further examined the benefit of vasopressin and steroids on survival to discharge with a favorable neurologic outcome, defined by Glasgow-Pittsburgh Cerebral Performance Category score of 1–2. A randomized, double-blind, placebo-controlled, parallel-group trial was performed at three centers in patients in cardiac arrest. Patients in the intervention group (VSE) received epinephrine with vasopressin (20 IU/CPR cycle for up to five cycles) and one 40-mg dose of methylprednisolone compared with epinephrine plus placebo in the control group. All survivors with postresuscitation shock after 4 hours were given stress-dose hydrocortisone (300 mg/d) with a subsequent taper. The primary outcome was return of spontaneous circulation of 20 minutes or longer and survival to hospital discharge with a favorable Cerebral Performance Category score of 1–2. Compared with the control group, patients in the VSE group had a higher probability of return of spontaneous circulation for 20 minutes or longer (109/130 [83.9%] vs. 91/138 [65.9%]; P = 0.005). Patients in the VSE group also had less epinephrine requirement, shorter advanced life support (ALS) duration and higher mean arterial pressure during and after CPR. The VSE group was more likely to be alive, with favorable neurological outcome on discharge (18/130 [13.9%] vs. 7/138 [5.1%]; P = 0.02). After resuscitation, 76/86 VSE survivors and 73/76 control survivors were given stressdose steroids for postresuscitation shock. Of these patients who survived 4 hours or longer, those in the VSE group were more likely to survive, with favorable neurologic outcome on discharge (16/76 [21.1%] vs. 6/73 [8.2%]; P = 0.02). With regard to secondary outcomes, patients in the VSE group had more neurologic and renal failure–free days, as well as ventilator-free days with improved mean arterial pressure and central venous oxygen saturation. Overall, this study demonstrates that the addition of vasopressin and steroids to ALS and stress-dose hydrocortisone in postresuscitation shock improved survival to discharge with more favorable neurologic outcomes compared with epinephrine and placebo. The positive primary and intermediate findings from this study support a causal pathway between vasopressin/steroid administration and improved recovery after cardiac arrest. Limitations of this study include the use of both vasopressin and steroids without the ability to assess the effects of either agent alone. In addition, follow up was limited to 60 days without the ability to evaluate longer-term neurologic outcome. Nevertheless, the neurological benefit suggested by this study is clinically substantial (number needed to treat = 11), and, given the extremely poor outcomes of in-hospital cardiac arrests, this study prompts discussions regarding modifications of the current ALS guidelines. n Author disclosures are available with the text of this article at

References 7. Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, Kolliantzaki I, Theodoridi M, Ischaki H, Makris D, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA 2013;310:270–279. 8. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S, Stathopoulos A, Kollintza A, Stamataki E, Roussos C. Vasopressin, epinephrine, and corticosteroids for inhospital cardiac arrest. Arch Intern Med 2009;169:15–24.

American Journal of Respiratory and Critical Care Medicine Volume 189 Number 8 | April 15 2014

Lung cancer screening, targeted temperature after cardiac arrest, and vasopressin and steroids in cardiac arrest.

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