Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

Background: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods: Fentanyl (5 mu g/kg bolus immediately followed by a 90 minute infusion of 3 mu g/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min). Also plasma samples for quantification of fentanyl were drawn. Results: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

Effect of Neonatal Asphyxia on the Impairment of the Auditory Pathway by Recording Auditory Brainstem Responses in Newborn Piglets: A New Experimentation Model to Study the Perinatal Hypoxic-Ischemic Damage on the Auditory Syste

Introduction Hypoxia-ischemia (HI) is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets. Method Hypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs) of newborn piglets exposed to acute hypoxia/ischemia (n = 6) and a control group with no such exposure (n = 10). ABRs were recorded for both ears before the start of the experiment (baseline), after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury. Results Auditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant. Conclusion The described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.

Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal Hypoxia-Ischemia

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Maitasunean eta errespetuan hezten: 0-3 urte bitartekoen harmonia

LABURPENA: Aurrerapen zientifikoek aurrera egin ahala, lehen haurtzarorako begirada eraldatu egin da, bereziki garapen motorraren alorrean. Haurtxoa izaki pasibo bezala ikusten zuten ikuskerek, subjektuaren konpetentzia goiztiarren aurrean begiruneko jarrerak gartu dituzte. Lan honetan kalitatezko hezkuntza eredu instituzionalizatua garatu zuen Emmi Pikler-en ekarpenak aztertuko ditugu. Eredu honek printzipio pedagogiko zehatz batzuen arabera jaioberria eta haurtxo txikia ikusteko beste era bat eta hezitzaile bezala zaintzen dugun ume bakoitzarekiko betetzen dugun rolaren eraldaketa proposatzen du. Honek hezitzailearen jardunbide tradizionala birplanteatzera bultzatzen gaitu, haurrenganako maitasuna eta begirunea oinarritzat duen hezkuntza sistema bat eraiki ahal izateko.

Edoskitzea, opioideoen ondoriozko abstinentzia sindrome neonatalaren tratamendu eraginkorra?

[EUS]Helburuak: Berrikuspen bibliografiko honen helburu orokorra edoskitzea opioideekiko abstinentzia sindrome neonatalaren sintomak arintzeko eraginkorra den aztertzea izango da, eta baita honek tratamendu farmakologikoaren beharra gutxitzen duen. Bestalde, metadona hartzen duten emakume hauen esneko metadona kontzentrazioa nolakoa den eta esne honen bitartez jaioberriari heltzen zaion kantitatea nolakoa den identifikatu nahi da. Metodologia: Artikuluen bilaketa egiteko, datu base desberdinak erabili dira, baina erabilitako azken 8 artikuluak Pubmed eta Ovid-sp-ekoak dira. Artikulu guztiak bat izan ezik, ingelesezkoak dira, gaztelaniaz aurkitutako artikulu kantitate eskasa dela eta. “Edoskitzea” , “abstinentzia sindrome neonatala” eta “metadona terapia" terminoak erabili dira bilaketa prozesuan. Ondorioak: Edoskitzea opioideekiko abstinentzia sindrome neonatala jasaten duten jaioberrientzat gomendagarria dela esan daiteke, ikerketa hauen arabera, abstinentziaren sintomak eta tratamendu farmakologikoaren beharra gutxitzen baititu. Gainera, esneko metadona kontzentrazioa eta jaioberriari honen bitartez heltzen zaion kantitatea oso txikiak dira. Hala ere, lanak limitazioa garrantzitsu bat du, ikerketetako laginak txikiak izatea.

Zein da NIDCAP programaren eragina jaioberri goiztiarren neurogarapenean epe luzera? Atalez atal aztertua

Jaioberri goiztiarra, haurdunaldiko 37. astea baino lehen jaiotzen den haur heldugabea da. Jaioberri hauen biziraupen tasa azken hamarkadetako aurrerapen medikoei esker (inkubagailuak, farmakoak…) igo da baina bere heldugabetasunaren eraginez jaioberri hauen %23-60ak ezintasunak eta jarrera zein hezkuntza asaldurak pairatzen dituzte. 1970. urtean Heidelise Alsek NIDCAPa, (“Newborn Individualized Developmental Care and Assessment Program”) asmatu zuen, jaioberri bakoitzaren garapenean laguntzeko helburuarekin, beharrezko arreta berezia eta bakoitzarentzako zainketa planean oinarrituz. Helburua: NIDCAP metodoarekin kontaktuan egon ziren jaioberri goiztiarren eragina, epe luzera, nerbio sistemaren garapeneko atal motorea, atal kognitiboa eta neurosentsoriala aztertzean datza. Metodologia: Azterketa bibliografiko hau egiteko, beharrezko informazio bilaketa orokorra egin da helburua finkatzeko. Ondoren, Pubmed datu basean beharrezko irizpideak zehaztuta ikerlanak kritikoki irakurri, ebidentzian oinarrituz 11 hautatu eta landu ostean (guztira 946 jaioberri goiztiar aztertuz) garatu da. Emaitzak eta azterketa: Ikerlanen arabera NIDCAP metodoaren eraginetan egon diren 4, 9 eta 12 hilabeteko haurrek atal motorea garatuagoa duten datuak daude baina 18 eta 24 hilabeteko umeetan aldiz, ez dira ebidentziazko daturik aurkitu NIDCAParen efektu onuragarriei buruz, bere eraginaren efektua luzarora desagertuz. NIDCAP ereduaren erabilerak kognizio atalaren garapenean onurak ekartzen dituen datuak daude 9 hilabeteko haurretan (helburuak zuzentzeko gaitasunean eta arreta mantentzeko gaitasunean) eta 8 urteko haurretan ere (bat-bateko prozesamenduan) baina 12 eta 24 hilabeteko adinarekin, aldiz, ez dira eraginik hauteman. Garapeneko atal neurosentsorialean, ebidentziazko artikulu bakar baten arabera NIDCAParen erabilerak 8 urteko umeen ikusmen eta ahalmen espazialean laguntzen du. Ondorioa: NIDCAP metodoak jaioberri goiztiarretan daukan eragin gomendagarria dauka atal kognitiboan eta ikusmenean, baina oso eragin urria dauka metodo eraginkorra izateko.

Dobutamine in Paediatric Population: A Systematic Review in Juvenile Animal Models

Objective: Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/ paediatric population. Methods: Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included. Results: Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions. Conclusion: There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.