title: Epinephrine and sodium bicarbonate during CPR following asphyxial cardiac arrest in rats.
abstract: Although high-dose epinephrine during CPR improves coronary perfusion pressure (CoPP) and rate of return of spontaneous circulation (ROSC) in some models, its impact on long term outcome (> or = 72 h) has not been evaluated. Previous studies of sodium bicarbonate (NaHCO3) therapy during CPR indicate that beneficial effects may be dependent on epinephrine (EPI) dose. We hypothesized that EPI and NaHCO3 given during CPR have a significant impact on long term outcome. One hundred male Sprague-Dawley rats were prospectively studied in a block randomized placebo controlled trial. Rats were anesthetized, paralyzed, mechanically ventilated, instrumented, and each underwent 10 min of asphyxia, resulting in 6.8 +/- 0.4 min of circulatory arrest. Resuscitation was performed by mechanical ventilation and manual external chest compressions. EPI 0.0 (placebo), 0.01, 0.1, or 1.0 mg/kg IV was given at the onset of CPR, followed by NaHCO3 0.0 (placebo) or 1.0 mEq/kg IV. Successfully resuscitated rats were monitored and ventilated for 1 h without hemodynamic support. Neurologic deficit scores (NDS), cerebral histopathologic damage scores (CHDS) and myocardial histopathologic damage scores (MHDS) were determined in rats that survived 72 h. EPI improved CoPP and ROSC in a dose-dependent manner up to 0.1 mg/kg. Rats receiving EPI 0.1 and 1.0 mg/kg during CPR exhibited prolonged post-ROSC hypertension and metabolic acidemia, increased A-a O2 gradient, and an increased incidence of post-ROSC ventricular tachycardia or fibrillation. Overall survival was lower with EPI 0.1 and 1.0 mg/kg compared to 0.01 mg/kg. Although NDS was significantly less with EPI 0.1 mg/kg compared to placebo, there was no difference in CHDS between groups. In contrast, MDS was significantly higher with EPI 0.1 mg/kg compared to placebo or EPI 0.01 mg/kg. There was an overall trend toward improved survival at 72 h in rats that received NaHCO3 which was most evident in the EPI 0.1 mg/kg group. We conclude that (1) EPI during CPR has a biphasic dose/response curve in terms of survival, when post-resuscitation effects are left untreated and (2) NaHCO3 doses greater than 1.0 mEq/kg may be necessary to treat the side-effects of high-dose EPI. Further work is needed to determine if treating the immediate post-resuscitation effects of high-dose EPI can prevent detrimental effects on long-term outcome.
authors.affiliation: Safar Center For Resuscitation Research, University of Pittsburgh, PA 15260, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Neumar
authors.forename: N G
authors.initials: NG
authors.lastname: Bircher
authors.forename: K M
authors.initials: KM
authors.lastname: Sim
authors.forename: F
authors.initials: F
authors.lastname: Xiao
authors.forename: K S
authors.initials: KS
authors.lastname: Zadach
authors.forename: A
authors.initials: A
authors.lastname: Radovsky
authors.forename: L
authors.initials: L
authors.lastname: Katz
authors.forename: E
authors.initials: E
authors.lastname: Ebmeyer
authors.forename: P
authors.initials: P
authors.lastname: Safar
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications; D016887:Cardiopulmonary Resuscitation; D002493:Central Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000008:administration & dosage / Q000627:therapeutic use*; D006323:Heart Arrest / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D017693:Sodium Bicarbonate; D004837:Epinephrine