Maximum Concentration and Time to Maximum Concentration of Epinephrine in a Porcine Cardiac Arrest Model (original) (raw)
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Analgesia & Resuscitation : Current Research, 2013
The ResQPod ® , an impedance threshold device (ITD), was developed to augment cardiac output during cardiopulmonary resuscitation (CPR). If an ITD used with CPR does in fact increase venous return and cardiac output, then the use of such a device should increase the maximum concentration (Cmax) of epinephrine in the plasma and decrease the time to maximum concentration (Tmax). To our knowledge, no studies have investigated the pharmacokinetics of epinephrine during CPR while using the ResQPod ® . The purpose of this study was to determine the effect of the ResQPod ® on plasma concentrations of epinephrine in swine undergoing CPR for cardiac arrest.
Comparison of intravenous and intranasal administration of epinephrine during CPR in a canine model
Annals of Emergency Medicine, 1992
Study objectives: Epinephrine improves coronary perfusion pressure during CPR. However, administration of epinephrine during CPR may be delayed or omitted if IV or endotracheal access is not established. Therefore, the objective of this study was to determine if intranasal administration of epinephrine during CPR would provide an alternate route of drug administration that is readily accessible and requires no special technical skills. Design and setting: Randomized blinded study performed in a controlled laboratory environment. Type of participants: Twenty mongrel dogs weighing 19.5 +4.6 kg. Interventions: All dogs received either IV epinephrine 0.015 mg/kg or intranasal epinephrine 14 mg per nostril. Phentolamine (5 mg per nostril) was administered intranasally one minute before nasal administration of epinephrine to improve absorption. Each dog underwent three minutes of ventricular fibrillation followed by seven minutes of CPR with a pneumatic chest compression device. Epinephrine was administered at two minutes into CPR. Measurements and main results: Seven dogs were excluded because of inadequate baseline coronary perfusion pressure or compression device displacement, leaving a total of 13 dogs for analysis (six IV epinephrine, seven intranasal epinephrine). Baseline coronary perfusion pressure (mean +SD) was similar for IV epinephrine and intranasal epinephrine (16.9 +7.1 mm Hg versus 18.2 +13.8 mm Hg, respectively, P = .84). For IV and intranasal epinephrine, coronary perfusion pressure increased to 21.4 +9.2 mm Hg and 24.4 + 18.7 mm Hg one minute after epinephrine, respectively (P= .73). Five minutes after epinephrine coronary perfusion pressure was 18.2 +8.7 mm Hg and 24.3 +13.9 mm Hg for IV epinephrine and intranasal epinephrine, respectively (P= .38). The rate of successful resuscitation was similar for both groups, five of seven dogs for intranasal epinephrine and four of six dogs for IV epinephrine (P= .66). Conclusion: Intranasal epinephrine has similar effects on coronary perfusion pressure and resuscitation compared with standard-dose IV epinephrine. Therefore, the nasal route for administration of epinephrine appears to be an acceptable alternate method of drug delivery 1 0/1125
BMC cardiovascular disorders, 2014
In current guidelines, prolonged cardiopulmonary resuscitation (CPR) mandates administration of repeated intravenous epinephrine (EPI) doses. This porcine study simulating a prolonged CPR-situation in the coronary catheterisation laboratory, explores the effect of EPI-administrations on coronary perfusion pressure (CPP), continuous coronary artery flow average peak velocity (APV) and amplitude spectrum area (AMSA). Thirty-six pigs were randomized 1:1:1 to EPI 0.02 mg/kg/dose, EPI 0.03 mg/kg/dose or saline (control) in an experimental cardiac arrest (CA) model. During 15 minutes of mechanical chest compressions, four EPI/saline-injections were administered, and the effect on CPP, APV and AMSA were recorded. Comparisons were performed between the control and the two EPI-groups and a combination of the two EPI-groups, EPI-all. Compared to the control group, maximum peak of CPP (Pmax) after injection 1 and 2 was significantly increased in the EPI-all group (p = 0.022, p = 0.016), in EPI...
Circulation, 1987
Although epinephrine has been shown to improve myocardial blood flow during cardiopulmonary resuscitation (CPR), the effects of standard as well as larger doses of epinephrine on regional myocardial blood flow have not been examined. In this study we compared the effects of various doses of epinephrine on regional myocardial blood flow after a 10 min arrest in a swine preparation. Fifteen swine weighing greater than 15 kg each were instrumented for regional myocardial blood flow measurements with tracer microspheres. Regional blood flow was measured during normal sinus rhythm. After 10 min of ventricular fibrillation, CPR was begun and regional myocardial blood flow was determined. Animals were then randomly assigned to receive 0.02, 0.2, or 2.0 mg/kg epinephrine by peripheral injection. One minute after drug administration, regional myocardial blood flow measurements were repeated. The adjusted regional myocardial blood flows (ml/min/100 g) for animals given 0.02, 0.2, and 2.0 mg/kg epinephrine, respectively, were as follows:
Annals of Emergency Medicine, 1988
Our study compared the effect of high-dose epinephrine with the pure alphaagonist phenylephrine on regional myocardial blood flow (MBF), myocardial oxygen delivery (MD02), myocardial oxygen consumption (MV02), and defibrillation rates during CPR. Fifteen swine weighing more than 15 kg were instrumented for measurement of regional MBF using radiolabeled tracer microspheres. Measurements of regional MBF, MD02, and MVO 2 were made during normal sinus rhythm. Ventricular fibrillation was induced and persisted for ten minutes. CPR was begun using a pneumatic compression device. Regional MBF, MD02, and MVO 2 were measured during CPR. Following three minutes of CPR, animals (N= 15) were allocated to one of three groups (n = 5): Group 1, epinephrine 0.2 mg/kg; Group 2, phenylephrine 0.1 mg/kg; or Group 3, phenylephrine 1.0 mg/kg. Measurements of regional MBF, MDO 2, and MVO 2 were repeated after drug administration. Extraction ratios, defined as MVOJMDO 2, were calculated during normal sinus rhythm, CPR, and after drug administration. Defibrillation was attempted 31/2 minutes after drug administration. There was no significant difference in MBE MDO 2, MVO 2, and extraction ratio during normal sinus rhythm and CPR for any of the groups. Total MBF following drug administration was 67.2 +_ 49.4 mL/min/lO0 g for the group receiving epinephrine 0.2 mg/kg; 7.0 ± 7.1 mL/min/IO0 g for the group receiving phenylephrine 0.I mg/kg; and 36.7 ± 21.1 mL/min/lO0 g for the group receiving phenylephrine 1.0 rag~ kg. The extraction ratios for animals receiving epinephrine 0.2 mg/kg, phenylephrine 0.1 rag~ g, and phenylephrine 1.0 mg/kg were 76.6 ± 10.5%, 94.6 ± 4.0%, and 90.7 + 7.5%, respectively. The extraction ratio for the group receiving epinephrine was significantly better than both phenylephrine groups (P = .01). Defibrillation rates for each group were 80%, 0%, and 0%, respectively. Our results suggest that epinephrine in doses higher than are currently recommended improves MBF and oxygen extraction ratios during CPR when compared with the pure alpha-agonist phenylephrine. /Brown CG, Taylor RB, Werman HA, Luu T, Ashton J, Hamlin RL: Myocardial oxygen delivery~consumption during cardiopulmonary resuscitation: A comparison of epinephrine and phenylephrine. Ann Emerg Med April 1988;17:302-308.]
After a century, Epinephrine's role in cardiac arrest resuscitation remains controversial
The American Journal of Emergency Medicine, 2021
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Resuscitation, 2012
Objectives: This study examined the effects of IV epinephrine administration on carotid blood flow and end tidal CO2 (ETCO2) production of a swine undergoing active compressiondecompression CPR with an impedance threshold device (ACD-CPR + ITD). Methods: Six female swine (32±1Kg) were anesthetized, intubated and mechanically ventilated. Intracranial, thoracic aorta and right atrial pressures were recorded via indwelling catheters. Carotid blood flow (CBF) was recorded via Doppler. ETC02, Sp02 and EKG were monitored. Vfib was induced and went untreated for 6 minutes. 3 minutes each of standard CPR (STD), STD-CPR+ITD and ACD-CPR+ITD was preformed. At minute 9 of the resuscitation, 40µg/Kg of IV Epinephrine was administered and ACD-CPR+ITD was continued for 1 minute. Statistical analysis was performed with a Paired t test. Results: Aortic pressure, calculated cerebral and carotid perfusion pressures increased from STD < STD+ITD < ACD-CPR+ITD (p=<.001). Epinepherine administered during ACD-CPR+ITD signficantly increased mean aortic (29±5vs42±12, p=0.01) cerebral (12±5 vs 22±10, p=0.01), and coronary perfusion pressures (8±7 vs 17±4, p=0.02); however, mean CBF and ETCO2 decreased (respectively 29±15 vs 14±7.0, p=0.03; 20±7 vs 18±6, p=0.04). Conclusions: The administration of epinepherine during ACD-CPR+ITD significantly increased markers of macrocirculation, while significantly decreasing ETCO2, a proxy for organ perfusion. While the calculated cerebral perfusion pressures increased, the directly measured CBF decreased. This calls into question the ability of calculated perfusion pressures to accurately reflect blood flow and oxygen delivery to end organs.
Is Epinephrine During Cardiac Arrest Associated With Worse Outcomes in Resuscitated Patients?
Journal of the American College of Cardiology, 2014
BACKGROUND Although epinephrine is essential for successful return of spontaneous circulation (ROSC), the influence of this drug on recovery during the post-cardiac arrest phase is debatable. OBJECTIVES This study sought to investigate the relationship between pre-hospital use of epinephrine and functional survival among patients with out-of-hospital cardiac arrest (OHCA) who achieved successful ROSC. METHODS We included all patients with OHCA who achieved successful ROSC admitted to a cardiac arrest center from January 2000 to August 2012. Use of epinephrine was coded as yes/no and by dose (none, 1 mg, 2 to 5 mg, >5 mg). A favorable discharge outcome was coded using a Cerebral Performance Category 1 or 2. Analyses incorporated multivariable logistic regression, propensity scoring, and matching methods. RESULTS Of the 1,556 eligible patients, 1,134 (73%) received epinephrine; 194 (17%) of these patients had a good outcome versus 255 of 422 patients (63%) in the nontreated group (p < 0.001). This adverse association of epinephrine was observed regardless of length of resuscitation or in-hospital interventions performed. Compared with patients who did not receive epinephrine, the adjusted odds ratio of intact survival was 0.48 (95% confidence interval [CI]: 0.27 to 0.84) for 1 mg of epinephrine, 0.30 (95% CI: 0.20 to 0.47) for 2 to 5 mg of epinephrine, and 0.23 (95% CI: 0.14 to 0.37) for >5 mg of epinephrine. Delayed administration of epinephrine was associated with worse outcome. CONCLUSIONS In this large cohort of patients who achieved ROSC, pre-hospital use of epinephrine was consistently associated with a lower chance of survival, an association that showed a dose effect and persisted despite postresuscitation interventions. These findings suggest that additional studies to determine if and how epinephrine may provide long-term functional survival benefit are needed.
Critical Care, 2020
Background Despite controversies, epinephrine remains a mainstay of cardiopulmonary resuscitation (CPR). Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. The primary objectives of this study were to determine if (1) epinephrine doses have a significant acute effect on CBF and cerebral tissue oxygenation during CPR and (2) if the effect of each subsequent dose of epinephrine differs significantly from that of the first. Methods One-month-old piglets (n = 20) underwent asphyxia for 7 min, ventricular fibrillation, and CPR for 10–20 min. Epinephrine (20 mcg/kg) was administered at 2, 6, 10, 14, and 18 min of CPR. Invasive (laser Doppler, brain tissue oxygen tension [PbtO2]) and noninvasive (diffuse correlation spectroscopy and diffuse op...