Heart attack Using adrenaline, the incidence of serious brain damage has doubled!

On July 18, 2018, the New England Journal of Medicine published a study:

Heart attack Using adrenaline, the incidence of serious brain damage has doubled!

Out-of-hospital cardiac arrest, after the use of adrenaline, almost does not increase their survival rate; even if survived, the probability of serious brain damage has nearly doubled. This article has caused an uproar in the medical community!

Adrenaline is one of the earliest applied vasoactive drugs and the drug of choice for cardiopulmonary resuscitation. Is it clinically dangerous to have a sudden cardiac arrest, is adrenaline so dangerous?

Why is adrenaline used for cardiopulmonary resuscitation?

Cardiac arrest is the most critical emergency in the clinic. After cardiac arrest, systemic blood flow is interrupted, and spontaneous circulation cannot be established normally.

The brain is the organ most susceptible to ischemia and hypoxia, followed by the heart. At normal body temperature, after 5 minutes of cardiac arrest, brain cells begin to undergo irreversible ischemic damage.

The primary goal of extracardiac compression is to achieve reperfusion of early coronary blood flow, allowing blood to preferentially supply brain and heart tissue. However, the cardiac output caused by extracardiac compression is too low, only 10% to 20% of normal cardiac output, 5% of normal coronary blood flow and 15% of normal cerebral blood flow.


Obviously, relying on extra-cardiac compression is far from guaranteeing the blood supply needs of important organs such as the heart and brain.

In this case, why not consider "vasoactive drugs"?

Vasoactive drugs can reduce the runoff of the distal aorta, increase the peripheral circulation resistance of the systemic circulation, and increase the diastolic blood pressure of the aorta, thereby further increasing the coronary perfusion pressure.

Adrenaline can directly stimulate the α and β receptors, and the cardiac vascular β1 receptor is excited, which can strengthen the myocardial contractility, increase the heart rate, increase the cardiac output, and act on the β-receptors on the coronary artery, causing coronary relaxation.

For this reason, adrenaline has been on the historical stage of cardiopulmonary resuscitation.

Adrenaline cardiopulmonary resuscitation "famous history"

As early as 1906, researchers such as George Crile introduced the first report on the application of adrenaline to cardiopulmonary resuscitation. George Crile also made it clear that during cardiopulmonary resuscitation, the patient's diastolic blood pressure should be maintained at 30-40 mmHg to ensure effective myocardial perfusion.

However, several studies have shown that almost all resuscitation failures when the aortic diastolic blood pressure is lower than 40 mmHg; above 40 mmHg, 80% of patients can recover successfully. At the same time, the success rate of cardiopulmonary resuscitation is also increased when the coronary perfusion pressure exceeds 15 mmHg.

In 1963, Joseph S. Redding et al. found through animal cardiopulmonary resuscitation experiments that a combination of adrenaline or adrenaline combined with a beta blocker can achieve 100% recovery success, but if alpha blockers are Only 27% of the combined use of adrenaline was successful.

It can be seen that although adrenaline has both α and β receptor stimulating drugs, in cardiopulmonary resuscitation, its effect on increasing heart and cerebral blood supply is mainly through the activation of α receptors.


So, can adrenaline be better than pure alpha receptor stimulants?

Brown et al. measured blood flow in the brain area and confirmed that phenylephrine is not as large as the increase in blood flow caused by adrenaline;

Jude et al. compared various vasoactive drugs and found that regardless of the dose size, adrenaline produced the greatest arteriovenous pressure gradient, and the incidence of ventricular arrhythmia after defibrillation was lower than norepinephrine.

These studies have laid the foundation for adrenaline as the drug of choice for resuscitation drugs and have been the most widely used drug for clinical rescue of cardiac arrest.

However, in recent years, the effectiveness of adrenaline on out-of-hospital cardiac arrest has been repeatedly questioned.

"Questioning" about adrenaline

Autonomic circulation recovery has been an important indicator for judging the success of cardiopulmonary resuscitation after cardiac arrest. Adrenaline can improve the recovery rate of spontaneous circulation and has been confirmed by a large number of animal experiments and clinical trials.

However, a number of animal experiments and clinical studies have shown that adrenaline can increase the rate of spontaneous circulation recovery in patients with cardiac arrest, but does not increase the hospital discharge rate and long-term survival rate.

Due to the sudden and serious life-threatening of cardiac arrest, it is limited by morality. This study is limited to animal experiments, clinical observational studies, standard doses and high-dose adrenaline, but there has been no randomized control. The trial can fully compare the role of adrenaline and placebo in the treatment and prognosis of out-of-hospital cardiac arrest.

Latest research results

To determine whether the use of adrenaline is safe and effective for patients with cardiac arrest, a multi-center, randomized, double-blind, placebo-controlled trial of up to 3 years was conducted at the call of the International Resuscitation Liaison Committee, and in July. The 18th issue was published in the New England Journal of Medicine.

The study showed a total of 4015 pre-hospital adrenaline patients, of which 130 (3.2%) survived on day 30, compared with 94 of the 3999 patients in the placebo group, with a 30-day survival rate of 2.4. % (unadjusted OR = 1.39, P = 0.02).

However, among patients who survived discharge, the incidence of severe brain injury in the experimental group (31%) was nearly double that of the placebo control group (17.8%).

The researchers point out that clinical decisions must balance the burden and benefits of treatment. The treatment of cardiac arrest is burdensome because resuscitation is an invasive procedure and there is a high risk of complications. However, in this trial, adrenaline was found to have little benefit to the patient, although a slight increase in survival over 30 days was associated with a higher incidence of severe brain injury in survivors.

Quality of life is often more important than just survival. If the chances of recovery are small or the risk of survival after brain injury is high, patients may be reluctant to undergo heavy treatment.

Medicine is an evidence-based science. As evidence-based evidence continues to increase, the use of adrenaline is more questionable, which may change our existing guidelines and medication habits.