Vasopressin, a non-adrenergic vasopressor, was once included in the standardized protocols for resuscitating patients experiencing cardiac arrest. Advanced Cardiovascular Life Support (ACLS) guidelines, set by organizations like the American Heart Association (AHA), define the treatment sequence for these life-threatening events. ACLS pharmacologic agents are designed to enhance blood flow to the heart and brain during cardiopulmonary resuscitation (CPR). Recommendations for these agents shift based on accumulating scientific evidence, leading to a significant change in the role of vasopressin within the cardiac arrest algorithm.
Vasopressin’s Historical Role in ACLS
Vasopressin was formally incorporated into ACLS protocols during the 2000 and 2005 guidelines updates. It was recognized as a potent peripheral vasoconstrictor, acting primarily through V1 receptors on vascular smooth muscle cells. This mechanism was attractive because it was distinct from adrenergic effects that increase myocardial oxygen demand. Vasopressin’s ability to raise blood pressure and improve coronary perfusion pressure during CPR was a major theoretical benefit.
It was introduced as a substitution option for the first or second dose of epinephrine. The recommended dose was a single administration of 40 units given intravenously or intraosseously. This single-dose regimen reflected its longer half-life compared to epinephrine, which requires dosing every three to five minutes. This alternative was considered for ventricular fibrillation (VF), pulseless ventricular tachycardia (pVT), and later extended to non-shockable rhythms.
The 2015 Guidelines: Consolidation of Vasopressors
The definitive change occurred with the publication of the 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. This update effectively removed vasopressin as a standalone treatment option from the adult cardiac arrest algorithm. This decision was a consolidation of vasopressor therapy intended to streamline the protocol.
The 2015 guidelines eliminated the option of substituting vasopressin for the first or second dose of epinephrine. The goal was to simplify the complex resuscitation algorithm. Having two separate vasopressor options that lacked clear superiority over one another was deemed an unnecessary complication.
A recommendation against the combined use of vasopressin and epinephrine was also made, as this combination did not offer an advantage over standard-dose epinephrine alone. The focus shifted to maximizing the effectiveness of the most well-established agent.
Clinical Rationale for Removing Vasopressin
The removal of vasopressin was driven by a thorough review of clinical trial data accumulated between the 2005 and 2015 guidelines. Studies comparing vasopressin to epinephrine, or the combination of both drugs, failed to show a consistent and meaningful benefit in patient-centered outcomes. Large randomized controlled trials did not demonstrate that using vasopressin resulted in improved survival to hospital discharge or better neurological outcomes.
The lack of superior evidence meant vasopressin did not provide a proven advantage over the simpler, existing standard of care with epinephrine. While some trials showed similar rates of Return of Spontaneous Circulation (ROSC), ROSC alone is considered a less meaningful endpoint than long-term survival with good neurological function.
The scientific consensus concluded that adding a second vasopressor complicated the resuscitation process without offering a clear therapeutic gain. Since the evidence base for vasopressin did not meet the standard of improving survival and patient quality of life compared to epinephrine, eliminating the drug simplified the algorithm.
Current Vasopressor Strategy in ACLS
The current Advanced Cardiovascular Life Support protocols, including the 2020 guidelines and subsequent updates, maintain epinephrine as the single, standard vasopressor for all cardiac arrest rhythms. Epinephrine is administered at a dose of 1 milligram intravenously or intraosseously every three to five minutes throughout the resuscitation attempt. This dosing interval is maintained for both shockable rhythms (VF/pVT) and non-shockable rhythms (pulseless electrical activity and asystole).
For non-shockable rhythms, epinephrine should be administered as soon as feasible to maximize the chance of a successful outcome. In shockable rhythms, it is typically given after initial defibrillation attempts have failed. The standardized use of a single vasopressor ensures consistency and reduces cognitive load for providers during the high-stress environment of a code.
While vasopressin is absent from the core adult cardiac arrest algorithm, it does have limited, non-routine applications in specific contexts. For most clinical scenarios, the current strategy emphasizes the timely and consistent administration of epinephrine alongside high-quality chest compressions and early defibrillation.