A clinical trial of the use of adrenaline in cardiac arrests has found that its use results in less than 1% more people leaving hospital alive — but almost doubles the risk of severe brain damage for survivors of cardiac arrest. The research raises important questions about the future use of adrenaline in such cases and will necessitate debate amongst healthcare professionals, patients and the public.
Each year 30,000 people sustain a cardiac arrest in the UK and less than one in ten survive. The best chance of survival comes if the cardiac arrest is recognised quickly, someone starts cardiopulmonary resuscitation (CPR) and defibrillation (electric shock treatment) is applied without delay.
The application of adrenaline is one of the last things tried in attempts to treat cardiac arrest. It increases blood flow to the heart and increases the chance of restoring a heartbeat. However it also reduces blood flow in very small blood vessels in the brain, which may worsen brain damage. Observational studies, involving over 500,000 patients, have reported worse long-term survival and more brain damage among survivors who were treated with adrenaline.
Despite these issues, until now, there have been no definitive studies of the effectiveness of adrenaline as a treatment for cardiac arrest. This led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to establish if adrenaline was beneficial or harmful in the treatment of cardiac arrest. This “Pre-hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest (PARAMEDIC2)” trial was undertaken to determine if adrenaline is beneficial or harmful as a treatment for out of hospital cardiac arrest.
The trial was funded by the National Institute for Health Research, sponsored by the University of Warwick and led by researchers in the University’s Clinical Trials Units — part of Warwick Medical School. The trial ran from December 2014 through October 2017. It was conducted in 5 National Health Service Ambulance Trusts in the United Kingdom, and included 8000 patients who were in cardiac arrest. Patients were allocated randomly to be given either adrenaline or a salt-water placebo and all those involved in the trial including the ambulance crews and paramedics were unaware which of these two treatments the patient received.
The results of the trial have now been published in the New England Journal of Medicine (NEJM) on Thursday 19th July 2018 in an article entitled “A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.”
Of 4012 patients given adrenaline, 130 (3.2%) were alive at 30 days compared with 94 (2.4%) of the 3995 patients who were given placebo. However, of the 128 patients who had been given adrenaline and who survived to hospital discharge 39 (30.1%) had severe brain damage, compared with 16 (18.7%) among the 91 survivors who had been given a placebo. In this study a poor neurological outcome (severe brain damage) was defined as someone who was in a vegetative state requiring constant nursing care and attention, or unable to walk and look after their own bodily needs without assistance.
The reasons why more patients survived with adrenaline and yet had an increased chance of severe brain damage are not completely understood. One explanation is that although adrenaline increases blood flow in large blood vessels, it paradoxically impairs blood flow in very small blood vessels, and may worsen brain injury after the heart has been restarted. An alternative explanation is that the brain is more sensitive than the heart to periods without blood and oxygen and although the heart can recover from such an insult, the brain is irreversibly damaged.
Professor Gavin Perkins Professor of Critical Care Medicine in Warwick Medical School at the University of Warwick (and the lead author on the paper) said:
“We have found that the benefits of adrenaline are small — one extra survivor for every 125 patients treated — but the use of adrenaline almost doubles the risk of a severe brain damage amongst survivors.”
“Patients may be less willing to accept burdensome treatments if the chances of recovery are small or the risk of survival with severe brain damage is high. Our own work with patients and the public before starting the trial identified survival without brain damage is more important to patients than survival alone. The findings of this trial will require careful consideration by the wider community and those responsible for clinical practice guidelines for cardiac arrest.”
Professor Jerry Nolan, from the Royal United Hospital Bath (and a co-author on the paper) said:
“This trial has answered one of the longest standing questions in resuscitation medicine. Taking the results in context of other studies, it highlights the critical importance of the community response to cardiac arrest. Unlike adrenaline, members of the public can make a much bigger difference to survival through learning how to recognise cardiac arrest, perform CPR and deliver an electric shock with a defibrillator. “
Heart Disease Common Among Firefighters Who Die Of Cardiac Arrest
Firefighters who died from cardiac arrest were much more likely than those who died of other causes to show signs of both atherosclerotic and hypertensive heart disease at autopsy, according to new research in Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.
Among firefighters, more job-related deaths stem from cardiac arrest than from any other cause. To understand which heart diseases affect firefighters who die of cardiac arrest, this study looked at autopsy reports for firefighters who had died in the line of duty. Results showed that the most common diseases were narrowed arteries, or coronary artery disease, and structural abnormalities. These abnormalities included an enlarged heart (cardiomegaly) and increased wall thickness (hypertrophy) of the heart’s primary chamber for pumping blood, or left ventricle.
“Firefighters face many dangers, but the greatest risk is from underlying cardiovascular disease in combination with the physiological strain that the work places on the firefighter,” said study lead author Denise L. Smith, Ph.D., Tisch Distinguished Professor and director of the First Responder Health and Safety Laboratory at Skidmore College in Saratoga Springs, New York.
“Medical screening is necessary to establish that a firefighter is healthy enough to do this strenuous work.”
In terms of specific risks, narrowing of the arteries, enlarged heart and prior heart attack all were all independently associated with a greatly increased likelihood of death from cardiac arrest than firefighters who died of other causes. Similarly, firefighters who had a prior heart attack were 6 times more likely to have a duty-related death. an enlarged heart or a prior heart attack.
The researchers looked at autopsy records for U.S. male firefighters who died on duty between 1999 and 2014. Of 627 total deaths, 276 resulted from cardiac arrest and 351 from trauma. At the time of death, the firefighters were between 18 and 65 years old.
In the United States, approximately 1 in 7 people will die of sudden cardiac arrest. The life-threatening condition occurs when the heart’s electrical system stops working properly. Symptoms include unresponsiveness and gasping for air or not breathing. Immediate medical treatment is critical, including CPR and calling 9-1-1.
Cardiac arrest differs from a heart attack, which occurs when a blockage prevents blood flow to the heart, although heart attack and other heart conditions can cause cardiac arrest. Since cardiac arrest often is the first sign of underlying heart disease, screening and treatment for common heart diseases are critical.
“Historically, screening has focused more on risk factors for coronary artery disease,” Smith said.
“While this screening remains essential, it is important that clinicians also consider testing to identify an enlarged heart and increased wall thickness.”
Several limitations could have affected the study’s results. Among these limitations were differences in autopsy descriptions of heart disease, the use of a cut-off weight for an enlarged heart, and lack of information about other risk factors such as smoking and high blood pressure.
To control risk factors, the American Heart Association recommends lifestyle changes known as Life’s Simple 7®: manage blood pressure, control cholesterol, reduce blood sugar, get active, eat better, lose weight and stop smoking.
Targeted And Population-Based Strategies Both Necessary For Blood Pressure Control
Hypertension, or high blood pressure, is the leading risk factor for heart disease, and improvements in both targeted and population-based strategies for blood pressure control can lead to better prevention and control of hypertension, according to a review paper published today in the Journal of the American College of Cardiology. This paper is part of an eight-part health promotion series where each paper will focus on a different risk factor for cardiovascular disease.
The prevalence of hypertension globally is high and continues to increase. High blood pressure is associated with an increased risk of stroke, ischemic heart disease, heart failure and noncardiac vascular disease, as well as other conditions.
“Hypertension is caused by a combination of genetic, environmental and social determinants,” said Robert M. Carey, MD, professor of medicine at the University of Virginia School of Medicine and lead author of the paper.
“While genetic predisposition is nonmodifiable and conveys lifelong cardiovascular risk, the risk for hypertension is modifiable and largely preventable due to a strong influence by key environmental and lifestyle factors.”
Modifiable lifestyle factors, which are gradually introduced in childhood and early adult life, include being overweight/obesity, unhealthy diet, high sodium and low potassium intake, insufficient physical activity and consumption of alcohol. Many adults do not change their lifestyle after being diagnosed with hypertension and sustaining any changes that are made can be difficult.
Social determinants such as race and socioeconomic status are also risk factors for hypertension. High blood pressure is more prevalent in black and Hispanic populations as well as poorer areas and certain geographical areas such as the southeastern U.S.
According to the authors, prevention and control of hypertension can be achieved through targeted and population-based strategies. The targeted approach is the traditional strategy used in health care practice and seeks to achieve a clinically important reduction in blood pressure for individual patients. The population-based strategy aims to achieve small reductions that are applied to the entire population, resulting in a small downward shift in the entire blood pressure distribution. Studies have shown that the population-based approach may be better at preventing cardiovascular disease compared with the targeted strategy.
Factors preventing successful hypertension control include inaccurate blood pressure measurement and diagnosis of hypertension, lack of hypertension awareness and access to health care, and proper hypertension treatment and control. Low rates of medication adherence is also a common problem.
“Challenges to the prevention, detection, awareness and management of hypertension will require a multipronged approach directed not only to high-risk populations, but also to communities, schools, worksites and the food industry,” Carey said.
In the review, the authors discuss the Chronic Care Model, a framework for redesigning health care and addressing deficiencies in the care of chronic conditions such as hypertension, which may offer strategies for overcoming barriers at the health system, physician, patient and community levels. It is a collaborative partnership among the patient, provider and health system that incorporates a multilevel approach for control of hypertension. The model includes six domains — decision support, self-management support, delivery design, information systems, community resources and health care systems — which have been shown to lead to activated patients, responsive health care teams, improved health services and treatment outcomes, and cost-effectiveness. It also recognizes a collaborative partnership between the patient, provider and the care team. Community groups and organizations also play a significant role in providing health care information and support to various populations. Connected health, such as telemedicine and telephone and mobile health interventions can also help deliver improved care to a of greater number of patients with hypertension.
“Remarkable progress has been made in the understanding of blood pressure as a risk factor for heart disease and improving approaches to the prevention and treatment of hypertension,” said Carey.
“However, further research is still necessary to optimize care for these patients.”
Clock Drawing Cognitive Test Should Be Done Routinely In Patients With High Blood Pressure
A clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to research presented today at ESC Congress 2018.
Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.
“The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment,” said study author Dr Augusto Vicario of the Heart and Brain Unit, Cardiovascular Institute of Buenos Aires, Argentina.
“Identifying these patients provides the opportunity to intervene before dementia develops.”
The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test compared to the Mini-Mental State Examination (MMSE) to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centres in Argentina. The average blood pressure was 144/84 mmHg, average age was 60 years, and 62% were women.
For the clock drawing test, patients were given a piece of paper with a 10 cm diameter circle on it. They were asked to write the numbers of the clock in the correct position inside the circle and then draw hands on the clock indicating the time “twenty to four.” Patients were scored as having normal, moderate, or severe cognitive impairment. The MMSE has 11 questions and produces a score out of 30 indicating no (24-30), mild (18-23), or severe (0-17) cognitive impairment.
The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%) compared to the MMSE (21%). Three out ten patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle aged patients.
Dr Vicario said:
“Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe. This disconnect leads to impaired ‘executive functions’ such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions.”
“Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study more than one-third of patients were at risk.”
Dr Vicario concluded:
“The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia.”
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