Sudden cardiac arrest is defined by the absence of signs of circulation (Utstein 2015). According to the American Heart Association and the American College of Cardiology, cardiac arrest is manifested as the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. It is associated with very high mortality and a high incidence of neurological injury to the survivors.

Each year more than 400,000 Americans succumb to death due to sudden cardiac arrest.  Globally, hundreds of thousands of people suffer cardiac arrest from which fewer than one in ten survive if the arrest occurs outside a hospital and around one in five if the arrest occurs inside a hospital (Girotra 2014; Nolan 2014).

Out-of-hospital cardiac arrest (OHCA) is an important health concern in aging societies. Survival chances for cardiac arrest patients, both in and out of the hospital, are fewer. Beyond rapid defibrillation for shockable rhythms and early initiation of effective chest compressions, there are few therapies that have reliably been shown to improve outcomes for cardiac arrest patients.

 Cardiopulmonary resuscitation (CPR) is one of the key treatment options for cardiac arrest patients. The initial goal of resuscitation is to restart the cardiac activity, described as achieving the return of spontaneous circulation (ROSC). However, amongst those people in whom ROSC is achieved, only about 25% to 50% survive going home from the hospital. The main causes of hospital deaths are severe brain injury and multi-organ failure (Laver 2004).

 Pharmacological agents play a central role in early resuscitation. Vasopressors are pharmacological interventions administered to cardiac arrest patients during advanced cardiovascular life support (ACLS), with the aim of enhancing aortic diastolic and coronary perfusion pressure, as well as coronary, cerebral, and vital organ blood flow, in order to achieve the return of spontaneous circulation (ROSC).

 

 

 

Pharmacotherapy of Vasopressin in Cardiac Arrest

Adrenaline (epinephrine) has been the preferred vasopressor used for reviving cardiac activity (resuscitation) for several decades; however, vasopressin, an antidiuretic hormone has been recommended as an alternative in recent years.

A recent study suggests better outcomes for patients treated with vasopressin than for those given epinephrine, in the out-of-hospital setting. Vasopressin administration increases cerebral blood flow and oxygenation and raises blood flow to other vital organs. Vasopressin has neither chronotropic nor inotropic effects on the heart and is not associated with myocardial ischemia, myocardial dysfunction, or arrhythmias. The relatively long half-life of vasopressin is advantageous for the administration of a single dose during resuscitation. 

 

 

 

Mechanism of Action of Vasopressin

Vasopressin is a naturally-occurring antidiuretic hormone. In high doses it acts as a potent peripheral vasoconstrictor via V1a receptors located on smooth muscle cells, resulting in increased systemic vascular resistance which raises coronary perfusion pressure, or by potentiating the effects of endogenous catecholamines which also increases systemic vascular resistance.

Vasopressin led to higher arterial pressures and greater coronary perfusion pressures and had more long-lasting effects than epinephrine. Coronary perfusion pressure correlates with the return of spontaneous circulation in human cardiac arrest. Vasopressin administration increases cerebral blood flow and oxygenation and raises blood flow to another vital organs.

Previous laboratory data suggested that vasopressin is superior to adrenaline in improving vital organ perfusion during CPR, and post-ROSC survival leads to better neurological outcomes.

 Compared with epinephrine, vasopressin has been associated with less deleterious changes in cerebral microvascular blood flow, less attenuation from acidosis, less tachyphylaxis and pulmonary vasoconstriction, as well as longer effect duration. The investigators suggested that vasopressin might be more effective than epinephrine because of a greater vasoconstrictor effect in the presence of hypoxia and acidosis and because of longer-lasting effects. Furthermore, epinephrine, but not vasopressin, might have serious deleterious effects by increasing myocardial oxygen consumption during cardiac arrest

Furthermore, vasopressin stimulates ACTH release and, in animal studies of cardiac arrest, the levels of ACTH and cortisol were higher after the administration of vasopressin compared with adrenaline. High endogenous vasopressin levels, as well as increased cortisol levels, have been associated with improved survival after cardiac arrest.

The effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.

In one randomized controlled clinical trial, the investigators compared the effect of 40 IU of vasopressin with 1 mg of epinephrine in 40 pre-hospital patients who had not responded to three CPR. Compared with epinephrine, the group that received vasopressin had a 50% increase in the number of admitted patients and a 66% increase in patients alive at 24 h. The American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) guidelines recommend vasopressin as an alternative to epinephrine for the treatment of cardiac arrest. This recommendation could lead to use of vasopressin for millions of cardiac arrests worldwide

A recent study suggested the combination of vasopressin and epinephrine increases coronary perfusion pressure, improves the return of spontaneous circulation (ROSC), increases survival, improves cerebral blood flow, increases diastolic aortic pressure and improves neurological outcomes compared to epinephrine or vasopressin alone. Administration of vasopressin and epinephrine during cardiopulmonary resuscitation might be an effective strategy to improve the outcome. 

 

 

 

Pharmacokinetics of Vasopressin 

Vasopressin must be administered parenterally because it is degraded by trypsin in the gastrointestinal tract. Vasopressin is metabolized primarily in the liver and kidneys and has a plasma half-life of 10 to 20 minutes. Vasopressin is predominantly metabolized and only about 6% of the dose is excreted unchanged in the urine. The onset of the pressor effect of vasopressin is rapid, peaking within 15 minutes. Vasopressin has a clearance of 9-25 mL/min/kg in patients with vasodilatory shock receiving 0.01-0.1 U/min of vasopressin. 

Parenteral 40 IU of vasopressin in cardiac patients causes potent vasoconstriction, which in turn leads to increased coronary and cerebral perfusion, aiming in reaching the return of spontaneous circulation (ROSC), increasing the chances of survival in cardiac discharged patients significantly.

 

 

 

 

References

1. Andreas Lundin1*, T. D. (2016). Drug therapy in cardiac arrest: a review. European Heart Journal – Cardiovascular Pharmacotherapy (, 54-75.

2. Clifton W. Callaway, M. P. (2016). Usefulness of Vasopressin Administered With Epinephrine During Out-of-Hospital Cardiac Arrest. The American Journal of Cardiolog, 1316-1321.

3. Finn J, J. I. (2019). Adrenaline and vasopressin for cardiac arrest (Review). Cochrane Library, 1-92.

4. Ian G Stiell, P. C. (2001). Vasopressin versus epinephrine for inhospital cardiac arrest:. The Lancet, 105-109.

5. Mathias J. Holmberg, M. S. (2019). Vasopressors during adult cardiac arrest: A systemic review and meta-analysis. European Resuscitation Council, 107-122.

6. Pierre-Yves Gueugniaud, M. P.-S. (2008). Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation. The new england journal o f medicine, 21-31.

7. Qiang Zhang, B. L. (2017). Efficacy of vasopressin-epinephrine compared to epinephrine alone for out of hospital. American Journal of Emergency Medicine, 6.

8. Spyros D. Mentzelopoulos, M. P., Sotirios Malachias, M., Christos Chamos, M., Demetrios Konstantopoulos, M., & Theodora Ntaidou, M. (2020). Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest. JAMA, 270-279.

9. Spyros D. Mentzelopoulos, M. P., Spyros G. Zakynthinos, M. P., & Maria Tzoufi, M. P. (2009). Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest. American Medical Association, 15-24.

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