28 Randomized European Multicenter Trial of Surfactant Replacement in Neonatal Respiratory Distress Syndrome (Rds): Single Versus Multiple Doses of Curosurf

Abstract

The use of ACV in pregnancy is not yet recommended for two main reasons : its safety has not been established and the,lack of studies on pharmacokinetics. In this paper, we have.reviewed data concerning nine pregnant women who was iven ACV in the perinatal period. Route of administration ani doses were as following : orally (0) 350 mg/8 hours (5), lntravenousl (IV) 5-10 mg/kg/8 hours ( 4 ) . Plasm? trough (T) and eak (P) fevels of ACV was deteroinated by radio~mmuno assay. At girth, plasma ACV levels were achieved in the mother and her offspring. P and T after IV were effective to inhiblt viral replication (17-41 pmol/l 1 22-1 36 umol/l) and hi her than in vitro ID 50 for Herpes'vi;adea'viruses (0.1-4 pmoY/l) ; whereas T and P ranged from 0.32 to 0, 59 pmol/l and from 1.79 to 3.78 pmol/l after 10 doses given orally. Furthermore steady state plasma level was not achieved even after 10 doses 0. The maternal foetal ratio of ACV level was approximately 1. No side effects were noted in newborns. Conclnsion : If this drug is felt,to be used in a pregnant.voman, IV administration seems to be advisable regarding it's efficacy. 0 administration requires more data about recommended dosage. Transplacental passa e of ACV occurs. Plasma ACV levels in the mother reflect probagly foetal ACV level. Fifteen very low birth weight I1tLBY1 children, nine appropriate for qeitati;i;al age in6A. aean birth weight 1302tIb4 g, gestational age 30t_1.5 neeksl, and six jrall for gestaticaa! aqe ISSR, aean birth neigih I:b3t117 g, qestatlonal age 35.35.5 weeks), xere studied at the age of 7-12 years, and coapared to trentysix age-, sex-, and height-latched healthy children, who were born at term (lean birth weight 3?2b+ib7 51. !lox of :Ce YLRY rhildren had developed chronic broncopullonary disease, The hab~tua! !ere1 of physical act~vity was not different in the YLBY and control Grcup. Pulronary function tests and progresirre exercise tests on treadlill were perforled. Forced v!tal caoacity, forced expiraiory ?oliiae at one second and forced expiratory flow between 251 and 751 of vital capaclty were in tb: norral range for all the subjects. No difference; were founo in aaxiwda oxyeen con'.um~tion (YO2 aaxl, anaerobic threshold IATI and #axiral heart rate between :he ASR !'lo2 lax - Lidoca~rcis either a convulsant or an anticonvulwnt drug, according to the plasmatic levels. W e used its anticonvulwnt effect in scizures of various etiology. Lidocairtinfusion (L.I.) was efficient in 19/29 full term (FT) and in 10/13 prcmaturc babies (PT) with seizures (confirmed by EEG) resisting to Phenobarbital and Diazepam therapy. L.1. was given at decreasing dosage (4 mg/kg/h, day 1; 3 mg/kg/h, day 2; 2 mg/kg/h,day 3; 1 mg/kg/h,day 4). After L.I. beginning : -seizures were controlled within 30 min. in 23 cases, aftcr 3 to 13 hours in 4 cases; -background EEG changed in some casts, immediatly or after a delay (up to 24 hours) into a very discontinuous pattern. In 2 cases L.I. alone did not control seizures, but an additional bolus (2 mg/Kg) was efficient ...

Non-Invasive Ventilation and Surfactant Therapy

“…PA has been approved for use with an initial dose of 200 mg/kg, and 100 mg/kg for subsequent doses, whereas, BE is used at 100 mg/kg, and CA at 105 mg/kg for first and subsequent doses. Treatment with higher doses has been shown to result in lower BPD and mortality, less intraventricular hemorrhage, longer duration of action, faster weaning of oxygen, less air leaks, longer half-life, and less need for re-dosing [78][79][80][81][82]. The European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants [83] recommend an initial dose of 200 mg/kg dose of PA for the treatment of RDS, which is also endorsed by the European Association of Perinatal Medicine.…”

Have we been down this road before?

“…5 The increased clinical efficacy of multiple doses of poractant alfa (200 mg kg -1 initial dose) was documented in a large European trial. 6 In addition, our preliminary data suggest that improved pulmonary function in the poractant-treated very premature infants with respiratory distress syndrome may reduce the number with clinically significant patent ductus arteriosus. 2 We agree with Dr Lutchman that the surfactant story is far from complete and that ideally a comprehensive series of definitive, randomized control trials of available surfactants, with appropriate power for subgroup analysis, be funded and conducted to assess relative efficacy of surfactant preparations and dosing on preterm infant morbidity and mortality.…”

Is there really a clinical difference in surfactant preparations?

“…5 The increased clinical efficacy of multiple doses of poractant alfa (200 mg kg -1 initial dose) was documented in a large European trial. 6 In addition, our preliminary data suggest that improved pulmonary function in the poractant-treated very premature infants with respiratory distress syndrome may reduce the number with clinically significant patent ductus arteriosus. 2 We agree with Dr Lutchman that the surfactant story is far from complete and that ideally a comprehensive series of definitive, randomized control trials of available surfactants, with appropriate power for subgroup analysis, be funded and conducted to assess relative efficacy of surfactant preparations and dosing on preterm infant morbidity and mortality.…”