epinephrine has been employed for cardiac resuscitation for approximately 100 years , although it is known that this drug increases myocardial oxygen consumption during cardiopulmonary resuscitation ( cpr ) and increases the likelihood of cardiac failure after restoration of spontaneous circulation . in contrast , vasopressin proved to be beneficial over epinephrine as regards improving coronary perfusion pressure during cpr and as regards improving neurological recovery in the cpr laboratory . it was then hoped that vasopressin may also be better than epinephrine in large prospective clinical cpr trials , but these assumptions could not be proven in an inhospital cpr trial in canada   and in an out - of - hospital cpr trial in europe . a large subgroup ( n = 732 ) in the european vasopressin trial   and a retrospective analysis of cpr patients from pittsburgh , pa , usa , however , suggested possible beneficial effects of a combination of vasopressin and epinephrine when given during cpr . this strategy is currently being studied in an ongoing , very large ( > 2,000 patients ) , out - of - hospital prospective cpr trial in france . the exciting retrospective study of grmec and mally from slovenia adds further support to the hypothesis that a combination of vasopressin and epinephrine given during cpr may be more effective than epinephrine alone . while the authors acknowledge limitations of their investigation , such as a lack of randomizing and subgroup analysis of myocardial infarction patients , it is very impressive that 530 patients were studied in a very difficult setting without any funding . this investigation is in full agreement with studies showing that adding vasopressin in catecholamine - refractory shock states was beneficial during cpr , vasodilatory shock , and hemorrhagic shock . similar to balanced anaesthesia , it may be valuable to combine two drugs during cpr instead of increasing the dose of one drug . accordingly , the slovenian data confirm that the cumulative epinephrine dosage was significantly lower when additional vasopressin was employed . if the authors had used 2  40 iu vasopressin i.v . instead of only 1  40 iu vasopressin i.v . , as in the present study , this effect would most probably have been even greater . disappointment about advanced cardiac life support drugs is probably due to both complex effects of global ischaemia during cpr   and our own lack of understanding about cpr treatment effects . while we know in the laboratory that only continuous , aggressive chest compressions are able to improve vital organ perfusion to levels that render successful defibrillation likely , we failed to enforce laboratory cpr quality on the streets and on the wards . insufficient cpr is unfortunately occurring very often in hospitals and in the emergency medical service ; for example , chest compressions were performed less than 50% of the available time , therefore greatly underutilizing cpr possibilities . if blood does not flow during cpr , a given vasopressor is less likely to reach the target organ arterial vasculature , rendering beneficial effects of advanced cardiac life support drugs less likely . in one study of ventricular fibrillation victims , 75% of the surviving patients had a return of spontaneous circulation without injection of a vasopressor ; the remaining 25% of patients who required a vasopressor indicated that , if basic life support does not restore spontaneous circulation , the general outcome is most probably poor . accordingly , once advanced cardiac life support drugs are necessary , rescuers need to understand that the chance the patient will be discharged from the hospital is < 10% . the recently published european resuscitation council cpr guidelines state that ' current evidence is insufficient to support or refute the routine use of any particular drug or sequence of drugs ' ; the respective cpr algorithm primarily recommends injection of 1 mg epinephrine every 35 minutes , while vasopressin may also be injected . in contrast , the approach of the american heart association cpr guidelines is more liberal , stating that ' one dose of vasopressin may replace either the first or second dose of epinephrine ' . a question arises : should vasopressin be injected during cpr based on results from a subgroup analysis and retrospective studies ? as already described , basic life support saves the ' best ' cardiac arrest patients ; any subsequent advanced cardiac life support intervention has a decreasing likelihood to restore spontaneous circulation over time . our strategy is to alternate between an initial injection of 1 mg epinephrine i.v . and a subsequent injection of 40 iu vasopressin i.v . every 35 minutes during cpr ( figure 1 ) , since it may combine both beneficial effects of combining two drugs and avoiding complications of injecting excessive dosages of one drug alone . similar to most cpr strategies , this approach is not yet backed up by a randomized controlled trial , but the next cpr attempt may be just moments away . data from a previous study   is being used for a vasopressin registration application process by aguettant ( lyon , france ) in europe . supported by the science foundation of the austrian national bank grant 11448 , vienna , austria . if basic life support does not result in spontaneous circulation , our strategy is to alternate between an initial injection of 1 mg epinephrine i.v . and a subsequent injection of 40 iu vasopressin i.v . every 35 minutes if return of spontaneous circulation does not occur , independently of the initial electrocardiographic ( ecg ) rhythm . in one study , not a single patient with asystole or pulseless electrical activity as the initial ecg rhythm survived to hospital discharge if  3 mg epinephrine were injected ; ventricular fibrillation patients tolerated higher epinephrine dosages . there is no clear evidence how many times a vasopressor should be given until cardiopulmonary resuscitation ( cpr ) efforts should be terminated if return of spontaneous circulation does not occur .
epinephrine given during cardiopulmonary resuscitation ( cpr ) may cause beta - mimetic complications in the postresuscitation phase . 
 vasopressin may be an alternative vasopressor drug during cpr . 
 a subgroup analysis of a large prospective cpr investigation and of retrospective cpr studies suggests that vasopressin may be especially beneficial when combined with epinephrine . 
 beneficial effects of adding vasopressin were observed in other catecholamine - refractory shock states as well , such as vasodilatory shock and haemorrhagic shock . in order to maximize effects of any vasopressor during cpr , rapid aggressive chest compressions must be ensured to maximize blood flow and to enable advanced cardiac life support drugs to reach the arterial vasculature . 
 we suggest alternating injections of 1 mg epinephrine i.v . and 40 iu vasopressin i.v . every 35 minutes during cpr until spontaneous circulation can be achieved or cpr efforts are terminated .