Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis

Andersen, Lars W.; Kurth, Tobias; Chase, Maureen; Berg, Katherine M.; Cocchi, Michael N.; Callaway, Clifton W.; Donnino, Michael W.

doi:10.1136/bmj.i1577

Cited by 89 publications

(81 citation statements)

References 63 publications

(69 reference statements)

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“…The time from collapse to drug treatment was on average 22 min. This is longer than the interval during in-hospital cardiac arrest (average 3 min) [9,10] and during the majority of animal cardiac arrest models (average 9.5 min) [26]. The timing is similar to a systematic review of time to drug administration across 17 studies [19.4 min (95% CI 12.8-25.9)] [27] and with more recent studies (range 13-24 min) [28][29][30][31].…”

Section: Discussionsupporting

confidence: 59%

“…One possible explanation for the failure of adrenaline to improve neurological outcomes may be if treatment is administered too late after the onset of cardiac arrest. This hypothesis is supported by animal studies [6][7][8] and observational studies of cardiac arrest both in-and out-of-hospital [9,10], which suggest better outcomes the earlier that adrenaline is administered. However, the findings of observational studies need to be interpreted with caution because of likely confounding.…”

Section: Introductionmentioning

confidence: 86%

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The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial

Perkins

Kenna

et al. 2020

Intensive Care Med

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Purpose: To examine the time to drug administration in patients with a witnessed cardiac arrest enrolled in the Pre-Hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) randomised controlled trial.Methods: The PARAMEDIC2 trial was undertaken across 5 NHS ambulance services in England and Wales with randomisation between December 2014 and October 2017. Patients with an out-of-hospital cardiac arrest who were unresponsive to initial resuscitation attempts were randomly assigned to 1 mg intravenous adrenaline or matching placebo according to treatment packs that were identical apart from treatment number. Participants and study staff were masked to treatment allocation.Results: 8016 patients were enrolled, 4902 sustained a witnessed cardiac arrest of whom 2437 received placebo and 2465 received adrenaline. The odds of return of spontaneous circulation decreased in both groups over time but at a greater rate in the placebo arm odds ratio (OR) 0.93 (95% CI 0.92-0.95) compared with the adrenaline arm OR 0.96 (95% CI 0.95-0.97); interaction OR: 1.03, 95% CI 1.01-1.05, p = 0.005. By contrast, although the rate of survival and favourable neurological outcome decreased as time to treatment increased, the rates did not differ between the adrenaline and placebo groups. Conclusion:The rate of return of spontaneous circulation, survival and favourable neurological outcomes decrease over time. As time to drug treatment increases, adrenaline increases the chances of return of spontaneous circulation. Longer term outcomes were not affected by the time to adrenaline administration. (ISRCTN73485024).

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 86%

The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial

Perkins

Kenna

et al. 2020

Intensive Care Med

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“…61 In contrast, early epinephrine for patients with shockable rhythms is associated with worse outcomes. 62 The combination of vasopressin and methylprednisolone during in-hospital cardiac arrest has been tested in 2 small randomized clinical trials, with promising results. 18,21 This combination of drugs is not recommended in the US or European guidelines because of insufficient evidence to support their use (see eTable 1 in Supplement 1 for an overview of ongoing randomized clinical trials).…”

Section: Resultsmentioning

confidence: 99%

In-Hospital Cardiac Arrest

Andersen

Holmberg

Berg

et al. 2019

JAMA

635

535

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IMPORTANCE In-hospital cardiac arrest is common and associated with a high mortality rate. Despite this, in-hospital cardiac arrest has received little attention compared with other high-risk cardiovascular conditions, such as stroke, myocardial infarction, and out-of-hospital cardiac arrest. OBSERVATIONS In-hospital cardiac arrest occurs in over 290 000 adults each year in the United States. Cohort data from the United States indicate that the mean age of patients with in-hospital cardiac arrest is 66 years, 58% are men, and the presenting rhythm is most often (81%) nonshockable (ie, asystole or pulseless electrical activity). The cause of the cardiac arrest is most often cardiac (50%-60%), followed by respiratory insufficiency (15%-40%). Efforts to prevent in-hospital cardiac arrest require both a system for identifying deteriorating patients and an appropriate interventional response (eg, rapid response teams). The key elements of treatment during cardiac arrest include chest compressions, ventilation, early defibrillation, when applicable, and immediate attention to potentially reversible causes, such as hyperkalemia or hypoxia. There is limited evidence to support more advanced treatments. Post–cardiac arrest care is focused on identification and treatment of the underlying cause, hemodynamic and respiratory support, and potentially employing neuroprotective strategies (eg, targeted temperature management). Although multiple individual factors are associated with outcomes (eg, age, initial rhythm, duration of the cardiac arrest), a multifaceted approach considering both potential for neurological recovery and ongoing multiorgan failure is warranted for prognostication and clinical decision-making in the Post–cardiac arrest period. Withdrawal of care in the absence of definite prognostic signs both during and after cardiac arrest should be avoided. Hospitals are encouraged to participate in national quality-improvement initiatives. CONCLUSIONS AND RELEVANCE An estimated 290 000 in-hospital cardiac arrests occur each year in the United States. However, there is limited evidence to support clinical decision making. An increased awareness with regard to optimizing clinical care and new research might improve outcomes.

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“…At-risk patients also included patients intubated at a later point, because the matching should not be dependent on future events. 16,17,21,22 For example, a patient intubated at minute 3 was matched with a patient who was at risk of intubation at minute 3 (ie, either a patient intubated after minute 3 or a patient never intubated). Replacement of controls was used to reduce the number of unmatched exposed patients.…”

Section: Methodsmentioning

confidence: 99%

Association Between Tracheal Intubation During Pediatric In-Hospital Cardiac Arrest and Survival

Andersen

Raymond

Berg

et al. 2016

JAMA

Self Cite

141

101

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IMPORTANCETracheal intubation is common during pediatric in-hospital cardiac arrest, although the relationship between intubation during cardiac arrest and outcomes is unknown.OBJECTIVE To determine if intubation during pediatric in-hospital cardiac arrest is associated with improved outcomes. DESIGN, SETTING, AND PARTICIPANTSObservational study of data from United States hospitals in the Get With The Guidelines-Resuscitation registry. Pediatric patients (<18 years) with index in-hospital cardiac arrest between January 2000 and December 2014 were included. Patients who were receiving assisted ventilation, had an invasive airway in place, or both at the time chest compressions were initiated were excluded. EXPOSURES Tracheal intubation during cardiac arrest. MAIN OUTCOMES AND MEASURESThe primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation and neurologic outcome. A favorable neurologic outcome was defined as a score of 1 to 2 on the pediatric cerebral performance category score. Patients being intubated at any given minute were matched with patients at risk of being intubated within the same minute (ie, still receiving resuscitation) based on a time-dependent propensity score calculated from multiple patient, event, and hospital characteristics. RESULTSThe study included 2294 patients; 1308 (57%) were male, and all age groups were represented (median age, 7 months [25th-75th percentiles, 21 days, 4 years]). Of the 2294 included patients, 1555 (68%) were intubated during the cardiac arrest. In the propensity score-matched cohort (n = 2270), survival was lower in those intubated compared with those not intubated (411/1135 [36%] vs 460/1135 [41%]; risk ratio [RR], 0.89 [95% CI, 0.81-0.99]; P = .03). There was no significant difference in return of spontaneous circulation (770/1135 [68%] vs 771/1135 [68%]; RR, 1.00 [95% CI, 0.95-1.06]; P = .96) or favorable neurologic outcome (185/987 [19%] vs 211/983 [21%]; RR, 0.87 [95% CI, 0.75-1.02]; P = .08) between those intubated and not intubated. The association between intubation and decreased survival was observed in the majority of the sensitivity and subgroup analyses, including when accounting for missing data and in a subgroup of patients with a pulse at the beginning of the event.CONCLUSIONS AND RELEVANCE Among pediatric patients with in-hospital cardiac arrest, tracheal intubation during cardiac arrest compared with no intubation was associated with decreased survival to hospital discharge. Although the study design does not eliminate the potential for confounding, these findings do not support the current emphasis on early tracheal intubation for pediatric in-hospital cardiac arrest.

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Early administration of epinephrine (adrenaline) in patients with cardiac arrest with initial shockable rhythm in hospital: propensity score matched analysis

Cited by 89 publications

References 63 publications

The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial

The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial

In-Hospital Cardiac Arrest

Association Between Tracheal Intubation During Pediatric In-Hospital Cardiac Arrest and Survival

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