Delays in Cardiopulmonary Resuscitation, Defibrillation, and Epinephrine Administration All Decrease Survival in In-Hospital Cardiac Arrest

Nicholas G. Bircher, M.D.; Paul S. Chan, M.D., M.Sc.; Yan Xu, Ph.D.


Anesthesiology. 2019;130(3):414-422. 

In This Article


Our study contains several novel results. First, the frequency of delay between the confirmation of pulselessness and the initiation of CPR was greater than our a priori expectation that CPR would begin immediately. We found that 5.7% (3,283 of 57,312) of patients did not have instantaneous initiation of CPR upon determination of a pulseless cardiac arrest (i.e., time to initiation of CPR of more than 0 min). Our second and most important finding was that delay in initiation of CPR reduces survival independent of subsequent delays in defibrillation or epinephrine administration. Although several other studies in this database have examined a potential effect of delay in the initiation of CPR,[4,7–10] none have found that effect.

The third novel finding is that both time to initiation of CPR and time from CPR to defibrillation are determinants of survival in patients with shockable in-hospital cardiac arrests. Thus, the expected survival advantage from early CPR can be severely reduced by subsequent delay in defibrillation, i.e., an inefficient resuscitation. Fourth, in the epinephrine group, although the influence of arrest interval[11] and delay in defibrillation[3,12] are well recognized, our analysis is the first to suggest that increasing the time from the initiation of CPR to the administration of epinephrine was associated with lower survival. It is well known that patients in the epinephrine group start with a very poor prognosis as compared with patients in the defibrillation group.[1–4] Attention to both prompt CPR and prompt epinephrine administration are particularly important for the management of in-hospital cardiac arrest, because pulseless electrical activity and asystole comprise up to 82% of all such arrests.[2,13] Fifth, the rate of decline in survival with time from CPR to therapy is quite large in the defibrillation group as compared with the epinephrine group (table 2; supplemental figs. 4 and 6, and, depicting the stepwise reduction in survival with increasing time from CPR to defibrillation and epinephrine treatment respectively).

The total time from determination of pulselessness to defibrillation in the setting of ventricular fibrillation has long been known to be a determinant of outcome both for in-hospital[3] and out-of-hospital cardiac arrest.[5,11,14–17] In the pre-hospital setting, as the total time to defibrillation increases, even though survival decreases, relative improvement associated with bystander CPR increases.[18] We observed a similar context sensitivity for in-hospital cardiac arrest, i.e., delay in CPR reduces the survival benefit of defibrillation even if the total time to defibrillation remains the same. Similarly, total time to epinephrine treatment is also known to be a determinant of outcome for out-of-hospital[19,20] as well as in-hospital cardiac arrest both in adults[4] and in children.[10] Our results are consistent with prior studies. The novel feature of our work is the explicit demonstration that after adjustment for time to initiation of CPR, the time from the initiation of CPR to epinephrine treatment is a determinant of survival.

Although there is considerable observational evidence from the prehospital setting that increasing duration of cardiac arrest before CPR lowers survival,[15–17,21] relatively few studies have examined delays in CPR in the in-hospital setting. Herlitz et al.[22] reported that if CPR was started within 1 min, survival was 33% as compared with 14% if CPR was started later. Hajbaghery et al.[23] reported that in all patients that survived to hospital discharge and all patients on the morning shift, CPR was started in 1 to 6 min. For the evening and night shifts, CPR was started in 1 to 6 min in 92 and 89% of patients, respectively. Survival to hospital discharge was 8.3, 4.8, and 3.6%, respectively, for day, evening, and night shifts. Forcina et al.[24] reported that in nursing units using standard defibrillators, median time to initiation of CPR was 0 (interquartile range, 0, 1), but in those units using automatic external defibrillators, median time to initiation of CPR was 0 (interquartile range, 0, 2; P = 0.08). Although they found that this trend toward increased time to initiation of CPR did not correlate directly with survival, there was a trend toward decreased survival in the automatic external defibrillator units (18%) as compared with the standard defibrillator units (23%, P = 0.09). Although the reported delays in our study are comparable to those in the literature, the use of a large database and risk-adjusted model provides stronger evidence that delay in CPR in in-hospital cardiac arrest decreases survival.

The total time from determination of pulselessness to either the first defibrillation attempt or to epinephrine treatment is a measure of two separate processes. The total time for each includes the time from pulselessness to the initiation of CPR and then the time from CPR initiation to either defibrillation or epinephrine administration. In our study, there was a graded reduction in survival for delays in defibrillation and epinephrine treatment, and the reduction in survival was made worse if CPR was also delayed. Delivery of CPR, defibrillation, and epinephrine treatment are team and system processes, as well as context-sensitive, i.e., the potential benefit of each therapy is partially dependent on the other therapies rendered concurrently or subsequently. Previous analyses have tended to focus on individual therapies rather than consider the relationship between therapies. A well-functioning team, however, will have been trained to provide CPR, defibrillation, and epinephrine administration in a rapid fashion. Reduction of delays requires prompt action, particularly by ward staff while awaiting the arrival of the code response team. We chose a simple performance-based (i.e., time to therapy) model to examine the impact of delays on survival. Although this model has the minor disadvantage of not grouping patients by initial rhythm, the necessary risk adjustment was accomplished by including initial rhythm as a covariate in our model. This model has the advantage that it identifies therapy that does not match the initial rhythm, i.e., defibrillation for nonshockable rhythms and epinephrine for shockable rhythms. Both delays and mismatch of therapy represent opportunities for both research to understand these problems as well as education to ameliorate them.

Limitations of this study include the absence of independent verification of the times recorded, as well as exclusions either because the computed values for times were beyond the range or because of missing values for survival. The lack of synchronization of clocks in hospitals may also lead to errors in times. Our analysis also was not designed to establish causal factors for delays and did not include other unknown factors that may influence timeliness of CPR or defibrillation and epinephrine treatment. These remain areas of active investigation within Get With The Guidelines–Resuscitation. In addition, because of the curvilinear nature of the relationships between delays and survival, the Hosmer–Lemeshow test (supplemental table 3,, detailing model evaluation) suggests that alternative statistical methods might yield a better model fit. Other limitations include lack of extensibility of our results to all hospitals based on the subgroup of hospitals represented in quality improvement registries such as Get With The Guidelines–Resuscitation.

In conclusion, we found that both delays in time to initiation of CPR and time from CPR to treatment with either defibrillation or epinephrine are associated with lower survival for patients with in-hospital cardiac arrest. Further research is needed to determine the impact of both benchmarking and training efforts for in-hospital cardiac arrest focused on accurately measuring and reducing delays in CPR and from CPR to defibrillation or epinephrine administration.