Enhancing 4th Chain of Survival, Focusing on Drugs During CPR
Kyung Woon Jeung1
1Department of Emergency Medicine, Chonnam National University Hwasun Hospital, Republic of Korea
Despite wide efforts to improve outcome after cardiac arrest, only a minority of patients with cardiac arrest survive. Various pharmacological treatments have been used for the treatment of cardiac arrest. In this presentation, we will review the significant studies to date on the major drugs used during cardiopulmonary resuscitation.
The use of epinephrine in treating cardiac arrest has been a key component of advanced cardiovascular life support (ACLS) algorithm since the early 1960’s. Until recently, data on the benefit of the drug came primarily from animal studies and observational studies. Perkins et al. recently provided the results of the PARAMEDIC2 trial – a large, randomized clinical trial (RCT) assessing the effectiveness of epinephrine in patients with out-of-hospital cardiac arrest (OHCA) . In this trial, epinephrine increased survival at 30 days. However, there was no significant difference between the epinephrine and placebo groups in the proportion of patients who survived until hospital discharge with favorable neurologic outcome because more survivors had severe neurologic impairment in the epinephrine group.
Vasopressin is the most widely investigated alternative to epinephrine. A number of RCT have been done to find out the possible beneficial effects of vasopressin over epinephrine, but most of them failed to show any benefit of vasopressin in cardiac arrest patients. Two RCT demonstrated that the combination of vasopressin, steroid, and epinephrine increased the rate of return of spontaneous circulation as well as the rate of survival to hospital discharge with good neurologic outcome compared to epinephrine in adult in-hospital cardiac arrest patients .
Amiodarone and lidocaine have been recommended by the ACLS guidelines to help promote successful defibrillation in refractory ventricular fibrillation or pulseless ventricular tachycardia. These recommendations were based on the two RCT, performed around 20 years ago. In these RCT, amiodarone improved the rate of survival to hospital admission compared with both placebo and lidocaine, but not the survival to hospital discharge. However, these trials were not powered to demonstrate benefit in the survival to hospital discharge. The Resuscitation Outcome Consortium performed an RCT that compared intravenous amiodarone, lidocaine, or placebo in adult patient with OHCA due to refractory ventricular fibrillation or pulseless ventricular tachycardia . The primary outcome measure was survival to hospital discharge. In this trial, neither amiodarone nor lidocaine resulted in significantly increased survival to hospital discharge over placebo.
In summary, the poor survival rates after OHCA do not seem to be improved by intravenous drug administration. At least for now, the first three links in the chain of survival appears far more important than intravenous drug administration during CPR.
 Perkins GD, Ji C, Deakin CD, et al. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med 2018;379:711-721.
 Mentzelopoulos SD1, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA 2013;310:270-9.
 Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med 2016;374:1711-22.