Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults

Hansen, Matthew; Schmicker, Robert H.; Newgard, Craig D.; Grunau, Brian; Scheuermeyer, Frank; Cheskes, Sheldon; Vithalani, Veer; Alnaji, Fuad; Rea, Thomas D.; Idris, Ahamed H.; Herren, Heather; Hutchison, Jamie; Austin, Mike; Egan, Debra; Daya, Mohamud

doi:10.1161/circulationaha.117.033067

Cited by 146 publications

(127 citation statements)

References 29 publications

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“…During in-hospital cardiac arrest, Donnino et al noted a stepwise reduction in survival and favourable neurological outcome with delays in adrenaline administration exceeding 1-3 min [10]. In OHCA, Hansen et al found that every minute delay to the administration of adrenaline decreased survival (OR 0.96, 95% CI 0.95-0.98) and favourable neurological outcomes (OR 0.94, 95% CI 0.89-0.98) [33]. By contrast, the present study was consistent with Ewy et al in finding no difference in longer term outcomes according to the time of adrenaline administration for patients with nonshockable rhythms [29].…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…This 1‐minute difference in epinephrine concentration may be a critical factor in the potential treatment of a patient with anaphylaxis because mismanagement of anaphylaxis with delayed recognition of allergic symptoms or delayed treatment with epinephrine can be fatal 3,39‐42 . Indeed, there is a negative correlation between the time to epinephrine treatment and a patient's rate of survival 17 . Thus, immediate treatment and epinephrine absorption is crucial in the treatment of anaphylaxis.…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, cost effectiveness and autoinjector availability are potential barriers for certain patients with severe allergy 12,16 . These patient concerns may lead to lack of or delayed epinephrine treatment, which decreases the rate of survival in the event of anaphylaxis 17 …”

Section: Introductionmentioning

confidence: 99%

Intranasal epinephrine in dogs: Pharmacokinetic and heart rate effects

Dretchen

Mesa

Robben³

et al. 2020

Pharmacology Res & Perspec

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Epinephrine is the standard of care for the treatment of severe allergy and anaphylaxis. Epinephrine is most often administered through the intramuscular (IM) route via autoinjector. The current study aimed to evaluate an alternative method of epinephrine treatment through intranasal (IN) delivery in dogs. The pharmacokinetic (PK) parameters of maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the plasma concentration‐time curve from 0 to 90 minutes (AUC0–90) were observed after IN epinephrine (2, 3, 4, 5, 10, and 20 mg) and IM epinephrine via autoinjector (0.15 and 0.3 mg) for 90 minutes. Heart rate effects were measured after IN (2 and 5 mg) and IM (0.15 and 0.3 mg) epinephrine administration. IN epinephrine (5 mg) demonstrated significantly greater plasma epinephrine concentration at 1 minute as compared with IM epinephrine (0.3 mg) (1.68 ± 0.65 ng/mL vs 0.21 ± 0.08 ng/mL, P = .03). There were no significant differences in Cmax, Tmax, and AUC0–90 between 2‐mg IN and 0.15‐mg IM epinephrine or between 5‐mg IN and 0.3‐mg IM epinephrine. IN epinephrine reduced heart rate increases, as compared to IM epinephrine. IN and IM epinephrine were both well‐tolerated. Overall, IN epinephrine demonstrated advantages over IM epinephrine, including the rapid increase in plasma epinephrine and lack of increased heart rate over time.

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“…Although some studies have reported that these procedures were less effective in providing good neurological prognoses, 11,12 two recent studies have shown that early performance of these procedures was useful in non-shockable rhythm patients. 17,18 In physicianstaffed ambulances, the use of adrenaline and endotracheal intubation might be initiated earlier than in EMS ambulances.…”

Section: Discussionmentioning

confidence: 99%

Association between physician‐staffed ambulances and patient prognoses after out‐of‐hospital cardiac arrests with respect to shockable and non‐shockable rhythms: a retrospective observational study in a southern area of Shiga Prefecture Japan

Kato

Fujino

Shiomi

et al. 2019

Acute Medicine & Surgery

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Aim Out‐of‐hospital cardiac arrests (OHCA) are a significant public health problem; to improve patients’ prognoses, various interventions, such as providing physician‐staffed ambulances, have been implemented. We aimed to examine whether physician‐staffed ambulances were associated with patients’ prognoses after OHCA with respect to first‐monitored rhythms. Methods This retrospective observational study was undertaken between 1 September 2011 and 31 December 2015, using data based on Utstein‐style guidelines. We extracted data on age, sex, first‐monitored rhythm (shockable or non‐shockable), presence of a witness, bystander cardiopulmonary resuscitation, time from call to arrival at the scene, out‐of‐hospital adrenaline administration, out‐of‐hospital intubation, return of spontaneous circulation before arrival at the hospital, and survival and neurological outcomes 30 days after OHCA, according to cerebral performance categories. We undertook logistic regression analyses to assess the association between physician‐staffed ambulances and patients’ prognoses. Results A total of 882 OHCA patients were eligible for this study. Physician‐staffed ambulances attended to 164 OHCA patients. Multivariable analysis found that in non‐shockable rhythm patients, physician‐staffed ambulances significantly improved good neurological outcome (odds ratio, 3.65; 95% confidence interval [CI], 1.28–10.50; P = 0.02), return of spontaneous circulation before arrival at the hospital (odds ratio, 2.68; 95% CI, 1.62–4.42; P < 0.001), and 30‐day survival (odds ratio, 2.90; 95% CI, 1.30–6.45; P = 0.009). However, physician‐staffed ambulances were not associated with patient prognoses in shockable rhythm patients. Conclusion Despite our study's limitations, physician‐staffed ambulances might be associated with good neurological outcomes in non‐shockable rhythm patients. Our observations could provide more appropriate prehospital treatment options for OHCA patients.

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Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults

Cited by 146 publications

References 29 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

Intranasal epinephrine in dogs: Pharmacokinetic and heart rate effects

Association between physician‐staffed ambulances and patient prognoses after out‐of‐hospital cardiac arrests with respect to shockable and non‐shockable rhythms: a retrospective observational study in a southern area of Shiga Prefecture Japan

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