Primecuts – This Week In The Journals

September 6, 2011

By Keri Herzog, MD

Faculty Peer Reviewed

Hurricane Irene came and went.  Its path of destruction brought flooding and powerful winds, forcing evacuations, causing loss of power and extensive structural damage. It was a time where we all came together, not only for our families and friends, but also for our patients, with common goals of preparedness and safety. The journals this week focused on our patients as well, our sicker patients, and how our initial care and preparedness can make a difference.

This week The New England Journal of Medicine focused on CPR. The strategy of a brief period of CPR with early analysis of rhythm was compared with the strategy of a longer period of CPR with delayed analysis of rhythm, in patients with out of hospital cardiac arrest [1]. The 2005 guidelines from the American Heart Association–International Liaison Committee on Resuscitation previously suggested that EMS personnel could provide 2 minutes of CPR before the first analysis of cardiac rhythm. This trial set out to determine if that really was the best approach. This was a cluster-randomized trial involving 9933 adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada. 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome (95% confidence interval, −1.1 to 0.7; P=0.59). Analyses of the data showed no survival benefit for either study group.

Also in the New England Journal this week, we continue to focus on cardiac resuscitation and potential life saving measures. Previous studies have suggested that the use of an impedance threshold device (ITD), a device designed to enhance venous return and cardiac output during CPR, may improve survival rates after cardiac arrest when used during CPR [2]. This randomized, double-blinded study compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR. 8718 patients were included in the analysis, 4345 were randomly assigned to treatment with a sham ITD, and 4373 were assigned to treatment with an active device. The primary outcome was survival to hospital discharge with satisfactory function. A total of 260 patients in the sham-ITD group and 254 patients in the active-ITD group met the primary outcome (95% CI, −1.1 to 0.8; P=0.71) which led to a conclusion that use of an ITD did not significantly improve survival among patients with out-of-hospital cardiac arrest receiving standard CPR.

In a study published in JAMA this week, rates of potentially unintentional discontinuation of medications (prescribed for chronic diseases) following hospital or ICU admission were evaluated, where the focus is often on acute events with multiple transitions in care [3]. In this cohort study, records from 1997 to 2009 of all hospitalizations and outpatient prescriptions in Ontario, Canada were studied and included 396,380 patients aged 66 years or older with continuous use of at least 1 of 5 medication groups prescribed for long-term use: statins, antiplatelet/anticoagulant agents, levothyroxine, respiratory inhalers, and gastric acid–suppressing drugs. Rates of medication discontinuation were compared across patients admitted to the ICU, patients hospitalized without ICU admission, and nonhospitalized patients (controls). The primary outcome was failure to renew the prescription within 90 days after hospital discharge. With ICU exposure, the AORs (adjusted odds ratio) ranged from 1.48 (95% CI, 1.39-1.57) for discontinuing statins in 14.6% of ICU patients to an AOR of 2.31 (95% CI, 2.07-2.57) for discontinuing antiplatelet/anticoagulant agents in 22.8% of ICU patients vs. the control group.  There were additional risks of medication discontinuation in 4 of 5 medication groups in ICU patients vs. hospitalizations without an ICU admission. Discontinuation of statins and antiplatelet/anticoagulant medications showed an elevated AOR for multiple secondary outcomes at one year, including: death, emergency department visit, or emergent hospitalization. This study reminds us of the importance of focusing on chronic medical conditions and medications even while in the acute care setting.

A novel prognostic indicator for use in patients with advanced cancer was evaluated and compared with clinicians’ overall estimates of survival in a study in the British Medical Journal this week [4]. This observational cohort study was carried out in 18 palliative care services in the UK and included 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. Main outcome measures of this study were performance of a composite model to predict whether patients were likely to survive for 0-13 days, 14-55 days, or  >55 days compared with actual survival and clinicians’ predictions. On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and BUN) independently predicted both two week and two-month survival. Absolute agreement between actual survival and PiPS (their prognostic model) predictions was 57.3% (after correction for over-optimism). All models performed as well as, or better than, clinicians’ estimates of survival. Therefore, in patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival.
Lastly, carvedilol is one of the most effective beta blockers for preventing ventricular tachyarrhythmias in heart failure, but the mechanisms underlying its antiarrhythmic benefits remain unclear. This was examined this week in a study in Nature Medicine [5], which demonstrated that spontaneous Ca2+ waves, also called store overload–induced Ca2+ release (SOICR), evoke ventricular tachyarrhythmias in individuals with heart failure.  Carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). In this study, a new SOICR-inhibiting, minimally beta-blocking carvedilol analog, VK-II-86, was developed. VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol. Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to our individual patients.

As we pick up the pieces and return to normalcy following hurricane Irene, the journals remind us of our patients, and how early interventions and preparedness can make a difference in their lives.

Dr. Herzog is a third-year resident at NYU Langone Medical Center

Peer reviewed by Deborah Shapiro, MD wife of the editor-in-chief, Clinical Correlations.

Image courtesy of Wikimedia Commons


1.  Stiell IG, Nichol G, Leroux BG, et al. Early versus Later Rhythm Analysis in Patients with Out-of-Hospital Cardiac Arrest.. N Engl J Med sep. 2011; 365:787-797.

2.  Aufderheide TP, Nichol G, Rea TD, et al. A trial of an impedence threshold device in out –of-hospital cardiac arrest. N Engl J Med 2011; 365:798-806.

3.  Bell CM, Brener SS, Gunraj N, et al. Association of ICU or hospital admission with unintentional discontinuation of medications for chronic diseases. JAMA 2011;306(8):840-847.

4.  Gwilliam B, Keeley V, Todd C, et al. Development  of prognosis in palliative care study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study. BMJ 2011; 343:d4920.

5.  Zhou Q, Xiao J, Jiang D, et al. Carvedilol and its new analogs suppress arrythmogenic store overload-induced Ca 2+ release. Nature Medicine July 2011; 1003-1009.