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Epinephrine before defibrillation in patients with shockable in-hospital cardiac arrest: propensity matched analysis.

ABSTRACT:

Objective

To determine the use of epinephrine (adrenaline) before defibrillation for treatment of in-hospital cardiac arrest due to a ventricular arrhythmia and examine its association with patient survival.

Design

Propensity matched analysis.

Setting

2000-18 data from 497 hospitals participating in the American Heart Association's Get With The Guidelines-Resuscitation registry.

Participants

Adults aged 18 and older with an index in-hospital cardiac arrest due to an initial shockable rhythm treated with defibrillation.

Interventions

Administration of epinephrine before first defibrillation.

Main outcome measures

Survival to discharge; favorable neurological survival, defined as survival to discharge with none, mild, or moderate neurological disability measured using cerebral performance category scores; and survival after acute resuscitation (that is, return of spontaneous circulation for >20 minutes). A time dependent, propensity matched analysis was performed to adjust for confounding due to indication and evaluate the independent association of epinephrine before defibrillation with study outcomes.

Results

Among 34 820 patients with an initial shockable rhythm, 9630 (27.6%) were treated with epinephrine before defibrillation, contrary to current guidelines. In comparison with participants treated with defibrillation first, participants receiving epinephrine first were less likely to have a history of myocardial infarction or heart failure, but more likely to have renal failure, sepsis, pneumonia, and receive mechanical ventilation before in-hospital cardiac arrest (P<0.0001 for all). Treatment with epinephrine before defibrillation was strongly associated with delayed defibrillation (median 3 minutes v 0 minutes). In propensity matched analysis (9011 matched pairs), epinephrine before defibrillation was associated with lower odds of survival to discharge (25.2% v 29.9%; adjusted odds ratio 0.81, 95% confidence interval 0.74 to 0.88; P<0.001), favorable neurological survival (18.6% v 21.4%; 0.85, 0.76 to 0.92; P<0.001), and survival after acute resuscitation (64.4% v 69.4%; 0.76, 0.70 to 0.83; P<0.001). The above findings were consistent in a range of sensitivity analyses, including matching according to defibrillation time.

Conclusions

Contrary to current guidelines that prioritize immediate defibrillation for in-hospital cardiac arrest due to a shockable rhythm, more than one in four patients are treated with epinephrine before defibrillation, which is associated with worse survival.

SUBMITTER: Evans E

PROVIDER: S-EPMC8579224 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo evaluate whether patients who experience cardiac arrest in hospital receive epinephrine (adrenaline) within the two minutes after the first defibrillation (contrary to American Heart Association guidelines) and to evaluate the association between early administration of epinephrine and outcomes in this population.DesignProspective observational cohort study.SettingAnalysis of data from the Get With The Guidelines-Resuscitation registry, which includes data from more than 300 hospitals in the United States.ParticipantsAdults in hospital who experienced cardiac arrest with an initial shockable rhythm, including patients who had a first defibrillation within two minutes of the cardiac arrest and who remained in a shockable rhythm after defibrillation.InterventionEpinephrine given within two minutes after the first defibrillation.Main outcome measuresSurvival to hospital discharge. Secondary outcomes included return of spontaneous circulation and survival to hospital discharge with a good functional outcome. A propensity score was calculated for the receipt of epinephrine within two minutes after the first defibrillation, based on multiple characteristics of patients, events, and hospitals. Patients who received epinephrine at either zero, one, or two minutes after the first defibrillation were then matched on the propensity score with patients who were "at risk" of receiving epinephrine within the same minute but who did not receive it.Results2978 patients were matched on the propensity score, and the groups were well balanced. 1510 (51%) patients received epinephrine within two minutes after the first defibrillation, which is contrary to current American Heart Association guidelines. Epinephrine given within the first two minutes after the first defibrillation was associated with decreased odds of survival in the propensity score matched analysis (odds ratio 0.70, 95% confidence interval 0.59 to 0.82; P<0.001). Early epinephrine administration was also associated with a decreased odds of return of spontaneous circulation (0.71, 0.60 to 0.83; P<0.001) and good functional outcome (0.69, 0.58 to 0.83; P<0.001).ConclusionHalf of patients with a persistent shockable rhythm received epinephrine within two minutes after the first defibrillation, contrary to current American Heart Association guidelines. The receipt of epinephrine within two minutes after the first defibrillation was associated with decreased odds of survival to hospital discharge as well as decreased odds of return of spontaneous circulation and survival to hospital discharge with a good functional outcome.

Project description:BACKGROUND:Prior studies have reported higher in-hospital survival with prompt defibrillation and epinephrine treatment in patients with in-hospital cardiac arrest (IHCA). Whether this survival benefit persists after discharge is unknown. METHODS:We linked data from a national IHCA registry with Medicare files and identified 36?961 patients ?65 years of age with an IHCA at 517 hospitals between 2000 and 2011. Patients with IHCA caused by pulseless ventricular tachycardia or ventricular fibrillation were stratified by prompt (?2 minutes) versus delayed (>2 minutes) defibrillation, whereas patients with IHCA caused by asystole or pulseless electric activity were stratified by prompt (?5 minutes) versus delayed (>5 minutes) epinephrine treatment. The association between prompt treatment and long-term survival for each rhythm type was assessed with multivariable hierarchical modified Poisson regression models. RESULTS:Of 8119 patients with an IHCA caused by ventricular tachycardia or ventricular fibrillation, the rate of 1-year survival was higher in those treated with prompt defibrillation than with delayed defibrillation (25.7% [1466 of 5714] versus 15.5% [373 of 2405]; adjusted relative risk [RR], 1.49; 95% confidence interval [CI] 1.32-1.69; P<0.0001). This survival advantage persisted at 3 years (19.1% versus 11.0%; adjusted RR, 1.45; 95% CI, 1.23-1.69; P<0.0001) and at 5 years (14.7% versus 7.9%; adjusted RR, 1.50; 95% CI, 1.22-1.83; P<0.0001). Of 28?842 patients with an IHCA caused by asystole/pulseless electric activity, the rate of 1-year survival with prompt epinephrine treatment was higher than with delayed treatment (5.4% [1341 of 24?885] versus 4.3% [168 of 3957]; adjusted RR, 1.20; 95% CI, 1.02-1.41; P=0.02), but this survival benefit was no longer present at 3 years (3.5% versus 2.9%; adjusted RR, 1.17; 95% CI, 0.95-1.45; P=0.15) and at 5 years (2.3% versus 1.9%; adjusted RR, 1.18; 95% CI, 0.88-1.58; P=0.27). CONCLUSIONS:Prompt defibrillation for IHCA caused by ventricular tachycardia or ventricular fibrillation was associated with higher rates of long-term survival throughout 5 years of follow-up, whereas prompt epinephrine treatment for asystole/pulseless electric activity was associated with greater survival at 1 year but not at 3 or 5 years. By quantifying the greater survival associated with timely defibrillation and epinephrine administration, these findings provide important insights into the durability of survival benefits for 2 process-of-care measures in current resuscitation guidelines.

Project description:ImportanceDelayed defibrillation (>2 minutes) in adult in-hospital cardiac arrest (IHCA) is associated with worse outcomes. Little is known about the timing and outcomes of defibrillation in pediatric IHCA.ObjectiveTo determine whether time to first defibrillation attempt in pediatric IHCA with a first documented shockable rhythm is associated with survival to hospital discharge.Design, setting, and participantsIn this cohort study, data were obtained from the Get With The Guidelines-Resuscitation national registry between January 1, 2000, and December 31, 2015, and analyses were completed by October 1, 2017. Participants were pediatric patients younger than 18 years with an IHCA and a first documented rhythm of pulseless ventricular tachycardia or ventricular fibrillation and at least 1 defibrillation attempt.ExposuresTime between loss of pulse and first defibrillation attempt.Main outcomes and measuresThe primary outcome was survival to hospital discharge. Secondary outcomes were return of circulation, 24-hour survival, and favorable neurologic outcome at hospital discharge.ResultsAmong 477 patients with a pulseless shockable rhythm (median [interquartile range] age, 4 years [3 months to 14 years]; 285 [60%] male), 338 (71%) had a first defibrillation attempt at 2 minutes or less after pulselessness. Children were less likely to be shocked in 2 minutes or less for ward vs intensive care unit IHCAs (48% [11 of 23] vs 72% [268 of 371]; P = .01]). Thirty-eight percent (179 patients) survived to hospital discharge. The median (interquartile range) reported time to first defibrillation attempt was 1 minute (0-3 minutes) in both survivors and nonsurvivors. Time to first defibrillation attempt was not associated with survival in unadjusted analysis (risk ratio [RR] per minute increase, 0.96; 95% CI, 0.92-1.01; P = .15) or adjusted analysis (RR, 0.99; 95% CI, 0.94-1.06; P = .86). There was no difference in survival between those with a first defibrillation attempt in 2 minutes or less vs more than 2 minutes in unadjusted analysis (132 of 338 [39%] vs 47 of 139 [34%]; RR, 0.87; 95% CI, 0.66-1.13; P = .29) or multivariable analysis (RR, 0.99; 95% CI, 0.75-1.30; P = .93). Time to first defibrillation attempt was also not associated with secondary outcome measures.Conclusions and relevanceIn contrast to published adult IHCA and pediatric out-of-hospital cardiac arrest data, no significant association was observed between time to first defibrillation attempt in pediatric IHCA with a first documented shockable rhythm and survival to hospital discharge.

Project description:BackgroundEpinephrine increases the chances of return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA), especially when the initial rhythm is non-shockable. However, this drug could also worsen the post-resuscitation syndrome (PRS). We assessed the association between epinephrine use during cardiopulmonary resuscitation (CPR) and subsequent intensive care unit (ICU) mortality in patients with ROSC after non-shockable OHCA.MethodsWe used data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing OHCA data located in the Greater Paris area, France) between May 2011 and December 2021. All adults with ROSC after medical, cardiac and non-cardiac causes, non-shockable OHCA admitted to an ICU were included. The mode of death in the ICU was categorized as cardiocirculatory, neurological, or other.ResultsOf the 2,792 patients analyzed, there were 242 (8.7%) survivors at hospital discharge, 1,004 (35.9%) deaths from cardiocirculatory causes, 1,233 (44.2%) deaths from neurological causes, and 313 (11.2%) deaths from other etiologies. The cardiocirculatory death group received more epinephrine (4.6 ± 3.8 mg versus 1.7 ± 2.8 mg, 3.2 ± 2.6 mg, and 3.5 ± 3.6 mg for survivors, neurological deaths, and other deaths, respectively; p < 0.001). The proportion of cardiocirculatory death increased linearly (R2 = 0.92, p < 0.001) with cumulative epinephrine doses during CPR (17.7% in subjects who did not receive epinephrine and 62.5% in those who received > 10 mg). In multivariable analysis, a cumulative dose of epinephrine was strongly associated with cardiocirculatory death (adjusted odds ratio of 3.45, 95% CI [2.01-5.92] for 1 mg of epinephrine; 12.28, 95% CI [7.52-20.06] for 2-5 mg; and 23.71, 95% CI [11.02-50.97] for > 5 mg; reference 0 mg; population reference: alive at hospital discharge), even after adjustment on duration of resuscitation. The other modes of death (neurological and other causes) were also associated with epinephrine use, but to a lesser extent.ConclusionsIn non-shockable OHCA with ROSC, the dose of epinephrine used during CPR is strongly associated with early cardiocirculatory death. Further clinical studies aimed at limiting the dose of epinephrine during CPR seem warranted. Moreover, strategies for the prevention and management of PRS should take this dose of epinephrine into consideration for future trials.

Project description:ObjectiveTo determine if earlier administration of epinephrine (adrenaline) in patients with non-shockable cardiac arrest rhythms is associated with increased return of spontaneous circulation, survival, and neurologically intact survival.DesignPost hoc analysis of prospectively collected data in a large multicenter registry of in-hospital cardiac arrests (Get With The Guidelines-Resuscitation).SettingWe utilized the Get With The Guidelines-Resuscitation database (formerly National Registry of Cardiopulmonary Resuscitation, NRCPR). The database is sponsored by the American Heart Association (AHA) and contains prospective data from 570 American hospitals collected from 1 January 2000 to 19 November 2009.Participants119,978 adults from 570 hospitals who had a cardiac arrest in hospital with asystole (55%) or pulseless electrical activity (45%) as the initial rhythm. Of these, 83,490 arrests were excluded because they took place in the emergency department, intensive care unit, or surgical or other specialty unit, 10,775 patients were excluded because of missing or incomplete data, 524 patients were excluded because they had a repeat cardiac arrest, and 85 patients were excluded as they received vasopressin before the first dose of epinephrine. The main study population therefore comprised 25,095 patients. The mean age was 72, and 57% were men.Main outcome measuresThe primary outcome was survival to hospital discharge. Secondary outcomes included sustained return of spontaneous circulation, 24 hour survival, and survival with favorable neurologic status at hospital discharge.Results25,095 adults had in-hospital cardiac arrest with non-shockable rhythms. Median time to administration of the first dose of epinephrine was 3 minutes (interquartile range 1-5 minutes). There was a stepwise decrease in survival with increasing interval of time to epinephrine (analyzed by three minute intervals): adjusted odds ratio 1.0 for 1-3 minutes (reference group); 0.91 (95% confidence interval 0.82 to 1.00; P=0.055) for 4-6 minutes; 0.74 (0.63 to 0.88; P<0.001) for 7-9 minutes; and 0.63 (0.52 to 0.76; P<0.001) for >9 minutes. A similar stepwise effect was observed across all outcome variables.ConclusionsIn patients with non-shockable cardiac arrest in hospital, earlier administration of epinephrine is associated with a higher probability of return of spontaneous circulation, survival in hospital, and neurologically intact survival.

Project description:BackgroundCurrent 2005 guidelines for advanced cardiac life support strongly recommend immediate defibrillation for out-of-hospital cardiac arrest. However, findings from experimental and clinical studies have indicated a potential advantage of pretreatment with chest compression-only cardiopulmonary resuscitation (CPR) prior to defibrillation in improving outcomes. The aim of this meta-analysis is to evaluate the beneficial effect of chest compression-first versus defibrillation-first on survival in patients with out-of-hospital cardiac arrest.MethodsMain outcome measures were survival to hospital discharge (primary endpoint), return of spontaneous circulation (ROSC), neurologic outcome and long-term survival. Randomized, controlled clinical trials that were published between January 1, 1950, and June 19, 2010, were identified by a computerized search using SCOPUS, MEDLINE, BIOS, EMBASE, the Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts database, and Web of Science and supplemented by conference proceedings. Random effects models were used to calculate pooled odds ratios (ORs). A subgroup analysis was conducted to explore the effects of response interval greater than 5 min on outcomes.ResultsA total of four trials enrolling 1503 subjects were integrated into this analysis. No difference was found between chest compression-first versus defibrillation-first in the rate of return of spontaneous circulation (OR 1.01 [0.82-1.26]; P = 0.979), survival to hospital discharge (OR 1.10 [0.70-1.70]; P = 0.686) or favorable neurologic outcomes (OR 1.02 [0.31-3.38]; P = 0.979). For 1-year survival, however, the OR point estimates favored chest compression first (OR 1.38 [0.95-2.02]; P = 0.092) but the 95% CI crossed 1.0, suggesting insufficient estimate precision. Similarly, for cases with prolonged response times (> 5 min) point estimates pointed toward superiority of chest compression first (OR 1.45 [0.66-3.20]; P = 0.353), but the 95% CI again crossed 1.0.ConclusionsCurrent evidence does not support the notion that chest compression first prior to defibrillation improves the outcome of patients in out-of-hospital cardiac arrest. It appears that both treatments are equivalent. However, subgroup analyses indicate that chest compression first may be beneficial for cardiac arrests with a prolonged response time.

Project description:For patients with in-hospital cardiac arrests attributable to nonshockable rhythms, delays in epinephrine administration beyond 5 minutes is associated with worse survival. However, the extent of hospital variation in delayed epinephrine administration and its effect on hospital-level outcomes is unknown.Within Get With The Guidelines-Resuscitation, we identified 103?932 adult patients (?18 years) at 548 hospitals with an in-hospital cardiac arrest attributable to a nonshockable rhythm who received at least 1 dose of epinephrine between 2000 and 2014. We constructed 2-level hierarchical regression models to quantify hospital variation in rates of delayed epinephrine administration (>5 minutes) and its association with hospital rates of survival to discharge and survival with functional recovery.Overall, 13?213 (12.7%) patients had delays to epinephrine, and this rate varied markedly across hospitals (range, 0%-53.8%). The odds of delay in epinephrine administration were 58% higher at 1 randomly selected hospital in comparison with a similar patient at another randomly selected hospital (median odds ratio, 1.58; 95% confidence interval, 1.51-1.64). The median risk-standardized survival rate was 12.0% (range, 5.4%-31.9%), and the risk-standardized survival with functional recovery was 7.4% (range, 0.9%-30.8%). There was an inverse correlation between a hospital's rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge (?=-0.22, P<0.0001) and survival with functional recovery (?=-0.14, P=0.001). In comparison with a median survival rate of 12.9% (interquartile range, 11.1%-15.4%) at hospitals in the lowest quartile of epinephrine delay, risk-standardized survival was 16% lower at hospitals in the quartile with the highest rate of epinephrine delays (10.8%; interquartile range, 9.7%-12.7%).Delays in epinephrine administration following in-hospital cardiac arrest are common and variy across hospitals. Hospitals with high rates of delayed epinephrine administration had lower rates of overall survival for in-hospital cardiac arrest attributable to nonshockable rhythm. Further studies are needed to determine whether improving hospital performance on time to epinephrine administration, especially at hospitals with poor performance on this metric, will lead to improved outcomes.

Project description:ImportanceDelay in administration of the first epinephrine dose is associated with decreased survival among adults after in-hospital, nonshockable cardiac arrest. Whether this association is true in the pediatric in-hospital cardiac arrest population remains unknown.ObjectiveTo determine whether time to first epinephrine dose is associated with outcomes in pediatric in-hospital cardiac arrest.Design, setting and participantsWe performed an analysis of data from the Get With the Guidelines-Resuscitation registry. We included US pediatric patients (age <18 years) with an in-hospital cardiac arrest and an initial nonshockable rhythm who received at least 1 dose of epinephrine. A total of 1558 patients (median age, 9 months [interquartile range [IQR], 13 days-5 years]) were included in the final cohort.ExposureTime to epinephrine, defined as time in minutes from recognition of loss of pulse to the first dose of epinephrine.Main outcomes and measuresThe primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation (ROSC), survival at 24 hours, and neurological outcome. A favorable neurological outcome was defined as a score of 1 to 2 on the Pediatric Cerebral Performance Category scale.ResultsAmong the 1558 patients, 487 (31.3%) survived to hospital discharge. The median time to first epinephrine dose was 1 minute (IQR, 0-4; range, 0-20; mean [SD], 2.6 [3.4] minutes). Longer time to epinephrine administration was associated with lower risk of survival to discharge in multivariable analysis (multivariable-adjusted risk ratio [RR] per minute delay, 0.95 [95% CI, 0.93-0.98]). Longer time to epinephrine administration was also associated with decreased risk of ROSC (multivariable-adjusted RR per minute delay, 0.97 [95% CI, 0.96-0.99]), decreased risk of survival at 24 hours (multivariable-adjusted RR per minute delay, 0.97 [95% CI, 0.95-0.99]), and decreased risk of survival with favorable neurological outcome (multivariable-adjusted RR per minute delay, 0.95 [95% CI, 0.91-0.99]). Patients with time to epinephrine administration of longer than 5 minutes (233/1558) compared with those with time to epinephrine of 5 minutes or less (1325/1558) had lower risk of in-hospital survival to discharge (21.0% [49/233] vs 33.1% [438/1325]; multivariable-adjusted RR, 0.75 [95% CI, 0.60-0.93]; P = .01).Conclusions and relevanceAmong children with in-hospital cardiac arrest with an initial nonshockable rhythm who received epinephrine, delay in administration of epinephrine was associated with decreased chance of survival to hospital discharge, ROSC, 24-hour survival, and survival to hospital discharge with a favorable neurological outcome.