A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European Epinephrine Study Group.

BACKGROUND: Clinical trials have not shown a benefit of high doses of epinephrine in the management of cardiac arrest. We conducted a prospective, multicenter, randomized study comparing repeated high doses of epinephrine with repeated standard doses in cases of out-of-hospital cardiac arrest. METHODS: Adult patients who had cardiac arrest outside the hospital were enrolled if the cardiac rhythm continued to be ventricular fibrillation despite the administration of external electrical shocks, or if they had asystole or pulseless electrical activity at the time epinephrine was administered. We randomly assigned 3327 patients to receive up to 15 high doses (5 mg each) or standard doses (1 mg each) of epinephrine according to the current protocol for advanced cardiac life support. RESULTS: In the high-dose group, 40.4 percent of 1677 patients had a return of spontaneous circulation, as compared with 36.4 percent of 1650 patients in the standard-dose group (P=0.02); 26.5 percent of the patients in the high-dose group and 23.6 percent of those in the standard-dose group survived to be admitted to the hospital (P=0.05); 2.3 percent of the patients in the high-dose group and 2.8 percent in the standard-dose group survived to be discharged from the hospital (P=0.34). There was no significant difference in neurologic status according to treatment among those discharged. High-dose epinephrine improved the rate of successful resuscitation in patients with asystole, but not in those with ventricular fibrillation. CONCLUSIONS: In our study, long-term survival after cardiac arrest outside the hospital was no better with repeated high doses of epinephrine than with repeated standard doses.

[Assessment of pharmacokinetic parameters of amikacin in a group of neutropenic patients in onco-hematology]. / Estimation des paramètres pharmacocinétiques de l'amikacine dans une population de patients neutropéniques en onco-hématologie.

The pharmacokinetics of Amikacin were studied in 56 febrile episodes for 45 patients with severe neutropenia while using the USC*Pack PC Clinical Programs for adaptive control of their dosage regimens [223 drug levels]. The purpose of this study are: i] to estimate the pharmacokinetic parameters in this neutropenic population [56 episodes, I], ii] to evaluate the effect of the dosage regimen: once-a-day [22 episodes, II] versus bid or tid [34 episodes, III]. Patients [mean age 53.3 +/- 17.9], 23 men and 22 women, received amikacin [17.7 +/- 3.6 mg/kg/d at day 1] in a 30 minutes infusion. The mean estimated creatinine clearance [CCr] was 76 +/- 22.5 ml/min/1.73 m2 at day 1. The method used for the population modeling was the Non Parametric EM algorithm [NPEM2] which computes the complete probability density function for a 1 or a 2 compartment model. The parametrizations studied are: Clearance/Volume [CL/VOL], Elimination rate constant/Volume [Kel/VOL] and KS/VS with Kel = KS * CCr + 0.00693, VS = VOL/Weight for a 1 compartment pharmacokinetic model. The main results concerned CL and VS with: CL[I] = 4.94 +/- 2.71, CL[II] = 4.74 +/- 2.65, CL[III] = 5.14 +/- 2.75 l/h and VS[I] = 0.31 +/- 0.11, VS[II] = 0.34 +/- 0.10, VS[III] = 0.30 +/- 0.11 l/kg. Volume of distribution VS is not so large as expected and a slight difference appears between II and III. The pharmacokinetic parameters obtained for this population of neutropenic patients will be used thereafter for the daily adaptive control of Amikacine therapy in our haematologic/oncologic patients. The variability observed remains important and requires an individualization of the dosage regimen for each patient.