Vasopressin in Cardiac Arrest Management?

Part 2

Despite years of scrutiny and research, survival rates for patients undergoing cardiopulmonary resuscitation remain at 5-15%. Some of the most recent pharmacological interventions under investigation (for possible consideration in ACLS guideline revisions to be published this fall) include the use of vasopressin as a vasopressor, amiodarone for the treatment of  ventricular fibrillation and tachycardia, and adenosine antagonists (i.e., theophylline) for bradyasystolic rhythms.

More innovative approaches include the use of thyroid hormone and endothelin. This article will concentrate on vasopressin, with future articles looking at other pharmacology and revisions in the technique of CPR itself. 

Epinephrine’s role in cardiac arrest is primarily for its alpha properties---vasoconstriction, and enhancing internal carotid and coronary perfusion. It’s beta-agonist properties are controversial in the peri-arrest state—increasing oxygen consumptive demands and reducing subendocardial vascular perfusion. ((Frishman, Vahdat, and Bhatta, 1998). Studies comparing pure alpha adrenergic agents have not shown that they are superior to epinephrine at restoring spontaneous circulation. Recent research  has identified a promising alternative to epinephrine—vasopressin.

As a hormone,vasopressin has roles as an antidiuretic, and in adrenocorticotropic hormone (ACTH)-releasing activity. Vasopressin is a potent vasoconstrictor that increases blood pressure and systemic vascular resistance, and decreases cardiac output, heart rate, left ventricular oxygen consumption, and myocardial contractility. With regard to cerebral blood flow, vasopressin not only increases flow to a greater degree than epinephrine, it also improves cerebral oxygenation and decreases venous hypercarbia (Prengal, Lindner, & Keller, 1996). 

Caution: this presents an issue currently being investigated and does not necessarily represent or advocate a change in guidelines for clinical practice. Additional investigation and consideration is required of the reader.

Vasopressin in refractory cardiac arrest

Back in 1996, investigators reported in the Annals of Internal Medicine about the startlingly successful use of  vasopressin  in the treatment of eight patients in cardiac arrest refractory to epinephrine and defibrillation. Patients were given 40 U of intravenous vasopressin followed by defibrillation. In all eight patients the defibrillation was successful,  and three of the eight were discharged from the with intact neurological function (the other five lived for 0.5-82 hours). 

Lindner KH, Prengel AW, Brinkmann A et al. Vasopressin administration in refractory cardiac arrest. Ann Intern Med 1996;124:1061—4.

Additional investigations pertaining to vasopressin use in cardiac arrest: 

Vasopressin decreases endogenous catecholamine plasma concentrations during cardiopulmonary resuscitation in pigs.

The purpose of this study was to evaluate the effect of vasopressin vs. saline placebo on catecholamine plasma concentrations during cardiopulmonary resuscitation (CPR) using 16 pigs in a laboratory setting.

After 15 mins of untreated cardiac arrest, and 3 minutes of CPR, the pigs were randomized to be treated with either 0.8 U/kg vasopressin  or placebo (normal saline). Arterial epinephrine and norepinephrine plasma concentrations were sampled at prearrest, after chest compressions, and  after drug administration during CPR.

RESULTS: In comparison with placebo pigs at 1.5 and 5 mins after drug administration, animals resuscitated with vasopressin had significantly  higher  left ventricular myocardial, total cerebral, and adrenal gland perfusion. Significantly lower mean epinephrine and norepinephrine plasma concentrations were detected in the vasopressin-treated pigs compared with the placebo group at 1.5 minutes and 5 minutes after drug administration.

CONCLUSIONS: Administration of vasopressin during CPR resulted in significantly superior vital organ blood flow, but significantly decreased endogenous catecholamine plasma concentrations when compared with placebo. 

Wenzel V; Lindner KH; Baubin MA; Voelckel WG, Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens-University of Innsbruck, Austria.  Crit Care Med 2000 Apr;28(4):1096-100

Medline record CITATION IDS: PMID: 10809289 UI: 20267286

The effects of repeated doses of vasopressin or epinephrine on  ventricular fibrillation in a porcine model of prolonged cardiopulmonary resuscitation

This study evaluated ventricular fibrillation mean frequency and amplitude to predict defibrillation success in a porcine cardiopulmonary resuscitation (CPR) model using repeated administration of vasopressin or epinephrine.

After 4 min of cardiac arrest and 3 min of CPR, 10 pigs were randomly assigned to receive either vasopressin or epinephrine, while another 11 animals were randomly allocated after 4 min of cardiac arrest and 8 min of CPR to receive every 5 min either vasopressin or epinephrine (vasopressin: 0.4 and 0. 8 units/kg, respectively; epinephrine: 45 and 200 mcg/kg). Ventricular fibrillation mean frequency and amplitude on defibrillation (as well as coronary perfusion pressure) were significantly higher in the vasopressin groups than in the epinephrine groups, respectively. All vasopressin animals were successfully defibrillated and survived (one hour) while none of the epinephrine-treated animals were.

CONCLUSIONS: Mean fibrillation frequency and amplitude predicted successful defibrillation and may serve as noninvasive markers to monitor continuing CPR efforts. Furthermore, vasopressin was superior to epinephrine in maintaining these variables above a threshold necessary for successful defibrillation. 

Achleitner U; Wenzel V; Strohmenger HU; Krismer AC; Lurie KG; Lindner KH; Amann, Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens-University of Innsbruck, Austria. Anesth Analg 2000 May;90(5):1067-75        

Medline: CITATION IDS: PMID: 10781454 UI: 20245112

Vasopressin improves survival after cardiac arrest in hypovolemic shock

Voelckel WG, Lurie KG, Lindner KH, Zielinski T, McKnite S, Krismer AC, Wenzel V. Cardiac Arrhythmia Center, Cardiovascular Division, Department of Medicine at the University of Minnesota, Minneapolis 55455.

"Survival after hypovolemic shock and cardiac arrest is dismal with current therapies. We evaluated the potential benefits of vasopressin versus large-dose epinephrine in hemorrhagic shock and cardiac arrest on vital organ perfusion, and the likelihood of resuscitation."

Using 18 pigs, one-third of their blood volume was removed over 15 minutes; ventricular fibrillation was induced 5 minutes later. After four minutes in cardiac arrest, standard CPR was initiated for an additional four minutes. Seven pigs were then given high dose (200 mcg/kg) of epinephrine, seven others received 0.8 units/kg of vasopressin, and the remaining four received a saline placebo. Two and one-half minutes later defibrillation was attempted. Subjects were observed for an additional one hour without intervention. Spontaneous circulation was restored in all pigs receiving medication (except one that had been given epinephrine) and none of the pigs that received the saline placebo. Researchers noted that the vasopressin-treated group had less acidosis, better organ perfusion and greater prolonged survival.

Post-recovery assessment of the neurological effects of vasopressin vs. epinephrine in pigs following prolonged cardiopulmonary resuscitation.

This study investigated the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in a porcine model undergoing prolonged cardiopulmonary resuscitation (CPR).

After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg), epinephrine (45, 45 and 200mcg/kg) or saline placebo.

The mean aortic diastolic pressure was significantly  higher after each of three vasopressin versus epinephrine versus saline placebo injections). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation.

RESULTS: All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived. Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology.

CONCLUSIONS: During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model. 

Wenzel V; Lindner KH; Krismer AC; Voelckel WG; Schocke MF; Hund W; Witkiewicz M; Miller EA; Klima G; Wissel J; Lingnau W; Aichner FT,  Department of Anesthesiology and Critical Care Medicine, The Leopold-Franzens-University of Innsbruck, Austria.  volker.wenzel@uibk.ac.at J Am Coll Cardiol 2000 Feb;35(2):527-33

CITATION IDS: PMID: 10676704 UI: 20139874

Assessing the effectiveness of vasopressin/epinephrine combination given during cardiac arrest  in porcine models.

Both epinephrine and vasopressin increase coronary perfusion pressure (CPP) when administered during cardiac arrest. Given their different mechanisms of action, this investigation tested the hypothesis that during cardiopulmonary resuscitation (CPR) a combination of vasopressin (0.3 U/kg)and epinephrine (40 mcg/kg) would be superior to either agent alone. 

Maximum CPP (diastolic aortic-right atrial pressures) during CPR was similar among the groups but the time course of action was different in each group: with epinephrine plus vasopressin the increase in CPP was significantly more rapid than with vasopressin alone whereas the CPP remained significantly higher for a longer periods of time with vasopressin or epinephrine/vasopressin combination versus epinephrine alone. 

Left ventricular blood flow (ml/min per g) determined during CPR two minutes after drug administration was similar between groups. At the same time, cerebral blood flow (ml/min per g) in the vasopressin group was more than two times higher compared with the other two groups.  Researchers concluded that  the combination of  vasopressin and epinephrine during cardiac arrest results in a more rapid rise in CPP when compared with vasopressin alone and a more sustained elevation in CPP than observed with epinephrine alone. Thus, the synergistic effects of these two potent vasopressor agents may be of benefit during CPR. 

Mulligan KA; McKnite SH; Lindner KH; Lindstrom PJ; Detloff B; Lurie KG, Cardiac Arrhythmia Center, University of Minnesota, Minneapolis 55455, USA. Resuscitation 1997 Nov;35(3):265-71    

 CITATION IDS: PMID: 10203408 UI: 99218071

Vasopressin combined with epinephrine decreases cerebral perfusion compared with vasopressin alone during cardiopulmonary resuscitation in pigs.

It is unknown whether a combination of vasopressin and epinephrine may be superior to vasopressin alone by targeting both nonadrenergic and adrenergic receptors. After 15 minutes of cardiac arrest (13 minutes of ventricular fibrillation and 2 minutes of pulseless electrical activity) and 3 minutes of chest compressions, 16 animals were randomly treated with either 0.8 U/kg vasopressin  or 0.8 U/kg vasopressin combined with 200 microg/kg epinephrine.

RESULTS: Comparison of vasopressin with vasopressin and epinephrine at 90 seconds and 5 minutes after drug administration resulted in comparable mean coronary perfusion pressures, cerebral perfusion pressure left ventricular myocardial blood flow, but significantly increased total cerebral blood flow(vasopression). Return of spontaneous circulation rates in both groups were comparable (vasopressin, 7 of 8; vasopressin and epinephrine, 6 of 8).

CONCLUSIONS: Comparison of vasopressin with vasopressin and epinephrine resulted in comparable left ventricular myocardial blood flow but significantly increased cerebral perfusion. 

Wenzel V; Linder KH; Augenstein S; Prengel AW; Strohmenger HU Department of Anesthesiology, University of Ulm, Germany. Volker.Wenzel@uibk.ac.at  Stroke 1998 Jul;29(7):1462-7; discussion 1467-8

Medline IDS: PMID: 9660404 UI: 98321841

A look at whether or not combining nitroglycerin with vasopressin enhances endocardial perfusion during cardiac arrest.

Although vasopressin increases vital organ blood flow during cardiopulmonaryresuscitation (CPR), endocardial perfusion remains suboptimal. This study was designed to assess the effects of vasopressin versus a combination of vasopressin and nitroglycerin on vital organ blood flow in a porcine model of CPR.

After 4 min of cardiac arrest, and 3 min of closed-chest compressions, 14 animals were randomly treated with either 0.4 U/kg vasopressin   or 0.4 U/kg vasopressin combined with 5 microg/kg nitroglycerin.

RESULTS: Coronary and cerebral perfusion pressure as well as left ventricular myocardial blood flow were comparable between groups throughout the experiment.

Ninety seconds after drug administration, vasopressin combined with nitroglycerin compared with vasopressin alone in significantly higher mean left ventricular endocardial blood flow and a significantly higher endocardial/epicardial perfusion ratio). Seven of seven animals in the vasopressin group, and four of seven animals in the vasopressin and nitroglycerin group (NS) were resuscitated successfully and survived the 2-h observation period.

CONCLUSION: Researchers concluded that, when compared with vasopressin therapy alone, combined vasopressin and nitroglycerin improved endocardial perfusion significantly immediately after drug administration during CPR. 

Wenzel V; Lindner KH; Mayer H; Lurie KG; Prengel A , Department of Anesthesiology, University of Ulm, Germany.     volker.wenzel@uibk.ac.at:     Resuscitation 1998 Jul;38(1):13-7 

Medline IDS: PMID: 9783504 UI: 98454825

This study presents a randomized comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation.

Studies in animals have suggested that intravenous vasopressin is associated with better vital-organ perfusion and resuscitation rates than is epinephrine in the treatment of cardiac arrest. Forty patients in ventricular fibrillation resistant to electrical defibrillation were prospectively and randomly assigned epinephrine (1 mg intravenously; n = 20) or vasopressin (40 U intravenously; n = 20) as primary drug therapy for cardiac arrest. The endpoints of this double blind study were successful  resuscitation (hospital admission), survival for 24 hours, survival to hospital discharge and neurological outcome (Glasgow coma scale).

RESULTS: Seven (35%) patients in the epinephrine group and 14 (70%) in the vasopressin group survived to hospital admission (p = 0.06). At 24 hours, four (20%) epinephrine-treated patients and 12 (60%) vasopressin-treated patients were alive (p =0.02). Three (15%) patients in the epinephrine group and eight (40%) in the vasopressin group survived to hospital discharge (p = 0.16). Neurological outcomes were similar (mean Glasgow coma score at hospital discharge 10.7  vs 11.7).

CONCLUSION: In this preliminary study, a significantly larger proportion of patients created with vasopressin than of those treated with epinephrine were resuscitated successfully from out-of-hospital ventricular fibrillation and survived for 24 hours. Based upon these findings, larger multicenter,studies of vasopressin in the treatment of cardiac arrest are needed. 

Lindner KH; Dirks B; Strohmenger HU; Prengel AW; Lindner IM; Lurie Department of Anesthesiology and Critical Care Medicine, University of Ulm, Germany. Lancet 1997 Feb 22;349(9051):535-7 

Medline IDS: PMID: 9048792 UI: 97200963

Additional Information: 

ACUTE CARE Director of Education's Vasopressin Links

ACLS2000.org's A Word On Vasopressin

Southwest EMS Education's Vasopressin page

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