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.

Disclosures

Anesthesiology. 2019;130(3):414-422. 

In This Article

Results

Demographic Data

Selected baseline characteristics of the patient groups treated with defibrillation and epinephrine are provided in table 1 (for a complete list see supplemental tables 2 and 4, http://links.lww.com/ALN/B829 and http://links.lww.com/ALN/B831, depicting a complete list of group baseline characteristics and their influence on survival, respectively). The median age in the overall cohort was 67 yr (interquartile range, 54, 78), 70.0% (40,130 of 57,312) were of white race; for 61.0% (34,935 of 57,312), in-hospital cardiac arrest occured in an intensive care unit. Of 57,312 patients, 44,241 were medical (77.2%) and 10,720 (18.7%) were surgical. Of patients treated initially with epinephrine, 94.3% (43,622 of 46,310) had a nonshockable cardiac arrest rhythm, whereas 83.0% (9,134 of 11,002) of defibrillated patients had a shockable cardiac arrest rhythm. A greater proportion of the epinephrine-treated group (table 1) were hypotensive at the time of cardiac arrest (defibrillation group 27.2% [2,990 of 11,002] vs. epinephrine group 36.7% [16,980 of 46,310]), had respiratory insufficiency (defibrillation group 36.6% [4,025 of 11,002] vs. epinephrine group 50.5% [23,360 of 46,310]), or required mechanical ventilation (defibrillation group 34.5% [3,799 of 11,002] vs.epinephrine group 41.6% [19,270 of 46,310]). The results of our exploratory analysis are presented in supplemental table 3 (http://links.lww.com/ALN/B830, detailing model evaluation), supplemental table 5 (http://links.lww.com/ALN/B832, detailing univariate analysis), supplemental tables 6–13 (http://links.lww.com/ALN/B833, http://links.lww.com/ALN/B834, http://links.lww.com/ALN/B835, http://links.lww.com/ALN/B836, http://links.lww.com/ALN/B837, http://links.lww.com/ALN/B838, http://links.lww.com/ALN/B839, http://links.lww.com/ALN/B840), and supplemental figs. 1 and 2 (http://links.lww.com/ALN/B841 and http://links.lww.com/ALN/B842, depicting multivariable pointwise analysis).

Overall Cohort (Groups Combined)

In our combined model, after multivariable adjustment, increasing time to initiation of CPR and time from CPR to treatment were associated with decreased survival (table 2). In the overall cohort of 57,312 patients, there were 9,802 survivors (17.1%; table 3). Times to initiation of CPR greater than 2 min were associated with a survival of 14.7% (91 of 618) as compared with 17.1% (9,711 of 56,694) if CPR was begun in 2 min or less (adjusted odds ratio [CI], 0.68 [0.54 to 0.87]; P < 0.002; table 2; Figure 2). Times from CPR to either defibrillation or epinephrine treatment of 2 min or less were associated with a survival of 18.0% (7,654 of 42,475), as compared with 15.0% (1,680 of 11,227) for 3 to 5 min, 12.8% (382 of 2,983) for 6 to 8 min, and 13.7% (86 of 627) for 9 to 11 min (reference, 0 to 2 min; for 3 to 5 min adjusted odds ratio, 0.83; CI, 0.78 to 0.88; P < 0.001, for 6 to 8 min adjusted odds ratio, 0.67; CI, 0.60 to 0.76; P < 0.001, and for 9 to 11 min adjusted odds ratio, 0.54; CI, 0.42 to 0.69; P < 0.001; table 2; Figure 3). There was a substantial difference between groups not only with respect to survival (38% [4,178 of 11,002] for patients treated with defibrillation vs. 12.1% [5,624 of 46,310] for patients treated with epinephrine, adjusted odds ratio, 0.41; CI, 0.37 to 0.44; P < 0.001; tables 2 and 3), but also in the rate at which survival is diminished with respect to time from CPR to either defibrillation or epinephrine therapy (overall effect P < 0.001, reference 0 to 2 min, for 3 to 5 min adjusted odds ratio, 0.66; CI, 0.59 to 0.75; P< 0.001, for 6 to 8 min adjusted odds ratio, 0.44; CI, 0.34 to 0.55; P < 0.001, and for 9 to 11 min, adjusted odds ratio, 0.31; CI, 0.25 to 0.44; P < 0.001; tables 2 and 3; supplemental figs. 4 and 6, http://links.lww.com/ALN/B844 and http://links.lww.com/ALN/B846, depicting the stepwise reduction in survival with increasing time to defibrillation and epinephrine treatment, respectively). This same model was tested using the generalized estimating equation and yielded very similar results (details in supplemental table 3, http://links.lww.com/ALN/B830, detailing model evaluation).

Figure 2.

Survival probability in the overall cohort with increasing time to initiation of cardiopulmonary resuscitation (CPR). Error bars represent unadjusted Clopper–Pearson binomial 95% CI.

Figure 3.

Survival probability in the overall cohort with increasing time from cardiopulmonary resuscitation (CPR) to treatment. Error barsrepresent unadjusted Clopper–Pearson binomial 95% CI.

Defibrillation Group

If CPR was begun in 2 min or less, survival was 38.1% (4,143 of 10,880) as compared with 28.7% (35 of 122) if CPR was begun in 3 to 6 min (adjusted odds ratio, 0.60; CI, 0.39 to 0.93, P = 0.023; table 2; supplemental Figure 3, http://links.lww.com/ALN/B843, depicting the reduction in survival with delayed CPR). Similarly, if defibrillation was attempted in 2 min or less, survival was 40.5% (3,530 of 8,713), as compared with 31.6% (508 of 1,608) at 3 to 5 min, 22.4% (100 of 447) at 6 to 8 min, and 17.1% (40 of 234) at 9 to 11 min (adjusted odds ratio, 0.79; CI, 0.69 to 0.90 for 3 to 5 min, adjusted odds ratio, 0.67; CI, 0.52 to 0.87 for 6 to 8 min, adjusted odds ratio, 0.51; CI, 0.35 to 0.75, overall effect; P < 0.001; table 2; supplemental Figure 4, http://links.lww.com/ALN/B844, depicting the decrease in survival with delayed defibrillation). If CPR and defibrillation were both delivered promptly (i.e., within 2 min), survival was 40.6% (3,503 of 8,628; table 3). If CPR was begun promptly, but defibrillation was delayed (followed CPR by more than 3 min), survival was 31.9% (504 of 1,582) for 3- to 5-min delay, 21.9% (97 of 442) for 6- to 8- min delay, and 17.1% (39 of 228) for 9- to 11-min delay (table 3). If CPR was delayed (i.e., begun after 3 to 6 min), survival was reduced to 31.8% (27 of 85) if defibrillation followed CPR by 0 to 2 min and 15.4% (4 of 26) if defibrillation followed CPR by 3 to 5 min (table 3).

Epinephrine Group

There was no difference in survival between patients who received CPR in 3 to 6 min (11.3% [56 of 496]) as compared with within 2 min (12.2% [5,568 of 45,814]; adjusted odds ratio, 0.75; CI, 0.56 to 1.00; P = 0.051; table 2; supplemental Figure 5, http://links.lww.com/ALN/B845, depicting survival with prompt vs. delayed CPR). There was a stepwise reduction in survival with each additional interval of delay from the initiation of CPR to epinephrine treatment: if epinephrine was administered within 2 min of initiation of CPR, survival was 12.2% (4,124 of 33,762) as compared with 12.2% (1,172 of 9,619; adjusted odds ratio, 0.88; CI, 0.82 to 0.95; P = 0.001) for 3 to 5 min and 11.2% (328 of 2,929; adjusted odds ratio, 0.75; CI, 0.66 to 0.85; P < 0.001; table 2; supplemental Figure 6, http://links.lww.com/ALN/B846, depicting the reduction in survival with increasing delay in epinephrine treatment). If both CPR and epinephrine were delivered promptly, survival was 12.2% (4,078 of 33,402), and if epinephrine was delayed by 3 to 5 or 6 to 9 min, survival was 12.2% (1,163 of 9,516) or 11.3% (327 of 2,896), respectively (table 3). If CPR was delayed (more than 2 min), survival was 12.8 (46 of 360), 8.7 (9 of 103), and 3.0% (1 of 33) for times to epinephrine of 0 to 2, 3 to 5, and 6 to 9 min, respectively (table 3).

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