Primecuts – This Week In The Journals

October 10, 2016

PrimeCuts 7 min read

Pumpkin_Spice_Latte_SignBy Samir Bhalla, MD

Peer Reviewed

October is upon us, which typically is notable for cooler weather, pumpkin spice lattes and playoff baseball. The focus this year, however, is the upcoming presidential election. Last week, Governor Mike Pence and Senator Tim Kaine faced off in the Vice Presidential debate at Longwood University in Virginia. Kaine was on the offensive, frequently bringing up many of the highly contested ideals and proposals of Donald Trump, while Pence did his best to refute these points. Many polls including that from CNN1 and the Washington Post reported Pence winning this round of debating, giving the republican party rejuvenation. This past week has also been notable for many interesting articles in the journals.

Therapeutic Hypothermia for In-Hospital Cardiac Arrest

Targeted temperature management(TTM) or hypothermia(TH) protocol was initially studied in out-of-hospital cardiac arrest patients due to ventricular fibrillation, and was shown to improve post-arrest neurological outcomes. The benefit of TH or TTM in PEA/asystole arrests or in-hospital cardiac arrest is not as well studies. However, the 2010 ACLS guidelines recommend therapeutic hypothermia for all adult post-cardiac arrest patients.

This week in JAMA, Chan et al2 published the results of a retrospective cohort study comparing outcomes between patients with in-hospital cardiac arrest who received hypothermia therapy versus those who did not. Over 26,000 patients were eligible for the study, however, 1524 patients who received hypothermia treatment were matched to 3714 patients who did not. Interestingly, the patients who received hypothermia protocol were more likely to have acute myocardial infarction and ventricular fibrillation as etiologies of their arrest and were less likely to have signs of additional end-organ damage (shock, respiratory failure, renal insufficiency, acute CVA, etc.) compared to patients who were not cooled. 27.4% of patients that were cooled survived to discharge compared to 29.2% of patients who were not cooled. When stratified, there was a statistically significant decreased survival in patients with non-shockable rhythms who were cooled compared to those who were not (ARR -3.2%; [95%, CI -6.2% to -0.3%]). There was a non-significant difference in survival between the groups for shockable rhythms. The incidence of death within the first 24hours following arrest was lower in the cooled group (29.1 vs 45.0%, P<.001). Neurological status was assessed using the cerebral performance category scoring system (1 equaling little residual neurological deficits and 5 equaling brain death). Patients who did not receive therapeutic hypothermia were more likely to have a cerebral performance category score of 1 or 2 (indicating persistent function for ADLs or better) compared to patients that received TH.

The results of this retrospective study suggest that therapeutic hypothermia may have adverse effects on survival and neurological outcome following in-hospital cardiac arrests due to both shockable and non-shockable rhythms. Given the relative widespread use of hypothermia post-cardiac arrest, further randomized prospective clinical trials are warranted to further investigate the risk/benefit of hypothermia following in-hospital cardiac arrest.

Zika Virus and Guillen-Barre Syndrome

Zika virus was originally described in 1952 in Uganda, however this mosquito transmitted virus has dominated news headlines over the past two years as outbreaks have developed in South and Central Americas, and in the Caribbean. Most infected patients are asymptomatic and those with symptoms generally experience mild flu-like symptoms. However, the concern with Zika stems from its complications, namely its association with birth defects and Guillen-Barre Syndrome(GBS). Previously a quiescent disease, French Polynesia experienced the first reported outbreak of Zika Virus in 2013. Shortly thereafter, there was an increase in the number of cases of GBS reported in French Polynesia suggesting a link. As outbreaks have arisen in the western hemisphere, there have similarly been reports of increased cases of GBS.

This week, NEJM published an observational study investigating the association between Zika and GBS in Colombia3. 68 patients presenting to hospitals in Zika endemic regions of Colombia with clinical symptoms consistent with GBS based on the Brighton criteria were studied. Of these patients, 66 (97%) had symptoms consistent with recent acute Zika virus infection (fever, rash, headches, myalgias, arthralgias, conjunctivitis) in the preceding 4 weeks. 42 of the patients had testing for Zika virus infection via PCR and anti-flavirvirus immunoglobulins of blood, CSF and urine. Of these 42, 17 (40%) met criteria for definitive diagnosis Zika virus infection with positive PCR analysis for the virus. 32 of the 42 patients tested has positive IgG or IgM CSF or serum serologies suggesting exposure to the Zika virus. It is important to note that these patients also demonstrated negative Dengue virus serologies. This study provides virologic and serologic support for the association between Zika virus infection and GBS.

Can Aspirin help prevent ARDS?

ARDS is a clinical syndrome characterized by diffuse lung injury and acute hypoxic respiratory failure. The pathogenesis of ARDS is postulated to relate to an inflammatory surge that results in damage to the junction between alveoli and pulmonary capillaries resulting in pulmonary infiltration, ventilation/perfusion mismatch, and profound hypoxemia. More recently, there has been research looking into the role of platelet activation in promoting endothelial injury through production of leukotrienes, thromboxane and prostaglandins. Thus platelets have been a recent focus in the treatment of ARDS and sepsis. Small observational studies have suggested a possible benefit to antiplatelet therapy such as aspirin in ARDS. To this end, Kor et al4. published the results of a randomized double blind placebo controlled clinical trial in JAMA this week investigating the benefit of aspirin in prevention of ARDS.

The study utilized the Lung Injury Prediction Score5(LIPS) which in previous studies has been shown to reliably predict patients at high risk for developing ARDS. The LIPS incorporates hypoxia, tachypnea, and predisposing factors such as sepsis, shock, aspiration, trauma, toxic inhalations and drowning. 400 patients admitted with LIPS score >4 were randomized to receive aspirin (325mg loading dose followed by 81mg daily) or placebo.

10.3% of patients in the aspirin group developed ARDS while 8.7% of patients in the placebo group, a non-significant difference (OR 1.24, [92.6% CI, 0.67-2.31], P=.53). Additionally, there were no significant differences in death within 28 days, death by 1 year, rates of mechanical ventilation, ventilator free days or hospital length. Patients receiving aspirin had a higher incidence of bleeding events (5.6%) compared to placebo group (2.6%) but this difference was also not statistically significant. Thus, the findings of this study suggest that aspirin does not reduce the risk of development of ARDS in high risk patients.

The Health Effects of Electronic Cigarettes

The extensive adverse effects of cigarette smoking and increasing bans on the public cigarette use have led to the rising popularity of electronic cigarettes in recent years. Many current users of E-cigarettes are former non-smokers and young adults under the age of 18. E-cigarettes allow for inhalation of nicotine that is aerosolized by electrical heating of a solvent. This allows for nicotine inhalation like smoking a cigarette but without the additional toxic components found in traditional cigarettes. The increasing popularity and use of E-cigarettes has led to questions about their safety and side effects. This week, Dinakar and O’Connor published a review article6 in NEJM investigating the health effects of E-cigarettes.

Mass spectroscopy has shown that solvents and aerosols, like those in E-cigarettes, contain many toxic components. Diactyl and acetyl propionyl are two components found in flavored E-cigarettes that have been associated with respiratory disease. Many in vitro assays have shown cytotoxic effects when cells are exposed to extracts of e-cigarette solvent or aerosol. In vivo studies in mice have shown E-cigarette exposure increases oxidative stress, cytokine levels, and pulmonary inflammation. However, two studies showed that when compared to tobacco smoke, E-cigarette extracts have less cytotoxic effects.

With regards to E-cigarettes impact on health at a macro-level, there are several considerations. First are the effects relating directly to the e-cigarette device itself.  This week in NEJM, Brownson et al7. published a report of 15 patients who sustained burn and blast injuries from the E-cigarette directly. Second is the effect of nicotine directly on the human body. While highly addictive and associated with tachycardia and hypertension, no studies have documented long term adverse health effects of nicotine outside of the prenatal period. Prenatal maternal nicotine use is associated with cognitive and behavioral deficits in the child. Therefore nicotine use via any route is not recommended for pregnant women.

Thus, the authors conclude that it is difficult to generate a safety profile for E-cigarettes given the wide variety in formulations and limited current research. There is data to suggest that E-cigarettes are likely safer than conventional cigarettes, but they are still more harmful than no cigarette use. As such the authors suggest regulations to make E-cigarettes unavailable to children and initiatives to discourage use in non-smokers. The authors call for more research into the efficacy of E-cigarettes for smoking cessation before their use can be recommended.

MINI-CUTS:

Hospitals are routinely evaluated on the rates of mortality and complications post myocardial infarction. This week in NEJM, Bucholz et al., evaluated the results of the converse relationship8. Patients who were admitted with myocardial infarction to highly performing hospital centers had an increased 30 day and long term survival compared to patients admitted to low performing hospitals.

Physical therapy and patient mobilization in the ICU setting is often limited by mechanical ventilation and patient attachment to monitors and drips. This week in Science Direct9, Schaller et al. demonstrated the results of a multi-disciplinary goal oriented focus on patient mobilization with strict oversight in the surgical intensive care unit. The intervention led to increased patient mobility, decreased ICU length of stay and increased functional independence at discharge.

Presidential election on your mind? This week NEJM published10,11 a series of articles discussing democratic and republican views on health care reform, and how the presidential election may impact our health care structure.

Dr. Samir Bhalla 3rd year Internal Medicine Resident at NYU Langone Medical Center

Peer reviewed by Ian Henderson, MD, contributing editor, Clinical Correlations, 3rd year Internal Medicine Resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons 

Resources:

  1. 1. Agiesta, Jennifer. “Pence edges Kaine in VP debate instant poll.” CNN.com. CNN 5 October 2016. http://www.cnn.com/2016/10/05/politics/mike-pence-tim-kaine-vp-debate-poll/index.html
  2. Chan PS, Berg RA, Tang Y, Curtis LH, Spertus JA, for the American Heart Association’s Get With the Guidelines–Resuscitation Investigators. Association Between Therapeutic Hypothermia and Survival After In-Hospital Cardiac Arrest.JAMA.2016;316(13):1375-1382. http://jama.jamanetwork.com.ezproxy.med.nyu.edu/article.aspx?articleid=2565288
  3. Parra B, Lizarazo J, et al. Gullain-Barre Syndrome Associated with Zika Virus Infection in Colombia. N Engl J Med 2016. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMoa1605564#t=article
  4. Kor DJ, Carter RE, Park PK, et al. Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial.JAMA.2016;315(22):2406-2414.  http://jama.jamanetwork.com.ezproxy.med.nyu.edu/article.aspx?articleid=2522739
  5. Zachary M. Bauman, Marika Y. Gassner, Megan A. Coughlin, Meredith Mahan, and Jill Watras, “Lung Injury Prediction Score Is Useful in Predicting Acute Respiratory Distress Syndrome and Mortality in Surgical Critical Care Patients.”Critical Care Research and Practice. 2015. https://www.hindawi.com/journals/ccrp/2015/157408/
  6. Dinaker C, O’Connor GT. The Health Effects of Electronic Cigarettes. N Engl J Med 2016;372: 1372-1381. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMra1502466
  7. Brownson EG, Thompson CM, et al. Explosion Injuries from E-Cigarettes. N Engl J Med 2016; 375:1400-1402. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMc1608478?query=featured_home
  8. Bucholz, et al. Life Expectancy after Myocardial Infarction, According to Hospital Performance. N Engl J Med 2016; 375:1332-1342 http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMoa1513223?query=featured_home
  9. Schaller, et al. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial The Lancet, Volume 388, Issue 10052, 1–7 October 2016, Pages 1377–1388. http://www.sciencedirect.com.ezproxy.med.nyu.edu/science/article/pii/S0140673616316373
  10. Oberlander, Jonathan. From Obamacare to Hillarycare — Democrats’ Health Care Reform Agenda. N Engl J Med 2016; 375:1309-1311 http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMp1610712?query=featured_home
  11. Wilensky, Gail R.What Would a Republican Win Mean for Health Policy? N Engl J Med 2016; 375:1312-1313 http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMp1610716?query=featured_home