Continuous-Infusion Vancomycin in Neonates: Assessment of a Dosing Regimen and Therapeutic Proposal

Introduction: Vancomycin remains the reference antibiotic in neonates for care-related infections caused by ß-lactam–resistant Gram-positive bacteria. Achieving the optimal serum vancomycin level is challenging because of high inter-individual variability and the drug's narrow therapeutic window. Continuous infusion might offer pharmacokinetic and practical advantages, but we lack consensus on the dosing regimen. The aim was to determine the proportion of neonates achieving an optimal therapeutic vancomycin level at the first vancomycin concentration assay and which dosing regimen is the most suitable for neonates.Methods: All neonates receiving continuous-infusion vancomycin (loading dose 15 mg/kg and maintenance dose 30 mg/kg/d) in a neonatal intensive care unit were retrospectively analyzed. The proportion of neonates reaching the target serum vancomycin level was calculated. After reviewing the literature to identify all published articles proposing a dosing regimen for continuous-infusion vancomycin for neonates, regimens were theoretically applied to our population by using maintenance doses according to covariate(s) proposed in the original publication.Results: Between January 2013 and December 2014, 75 neonates received 91 vancomycin courses by continuous infusion. Median gestational age, birth weight, and postnatal age were 27 weeks (interquartile range 26–30.5), 815 g (685–1,240), and 15 days (9–33). At the first assay, only 28/91 (30.8%) courses resulted in vancomycin levels between 20 and 30 mg/L (target level), 23/91 (25.3%) >30 mg/L and 40/91 (43.9%) <20 mg/L. We applied six published dosing regimens to our patients. One of these dosing regimens based on corrected gestational age (CGA) and serum creatinine level (SCR) would have allowed us to prescribe lower doses to neonates with high vancomycin levels and higher doses to neonates with low levels.Conclusions: A simplified dosing regimen of continuous-infusion vancomycin did not achieve therapeutic ranges in neonates; a patient-tailored dosing regimen taking into account CGA and SCR level or an individualized pharmacokinetic model can help to anticipate the inter-individual variability in neonates and would have been more suitable

Hydrocortisone post natale à visée respiratoire (comparaison bicentrique chez des prématurés nés à moins de 27 semaines)

Le traitement par dexaméthasone pour prévenir la dysplasie broncho-pulmonaire (DBP) entrave le développement cérébral. La littérature suggère l efficacité pulmonaire de l hydrocortisone (HC) sans effet neurologique néfaste.Comparer l évolution à court terme et à 2 ans de prématurés nés dans 2 centres de néonatologie aux pratiques différentes sur la corticothérapie post-natale: l un permissif, l autre restrictif. Etude rétrospective bicentrique de 2005 à 2008 incluant des prématurés nés à moins de 27 semaines d aménorrhée (SA) ventilés à J14. Le centre 1 utilisait un protocole HC, le centre 2 n utilisait pas ou qu exceptionnellement des corticoïdes. Les caractéristiques néonatales, les effets à court terme et à 2 ans ont été recueillis.107 patients inclus dans le centre 1, 113 dans le centre 2. 62 intubés dans le centre 1, 48 dans le centre 2 à J14. 57 patients du centre 1 et 6 patients du centre 2 ont reçu des corticoïdes systémiques. La durée de ventilation invasive et la mortalité étaient similaires. La durée de ventilation non invasive (VNI) (24 10 vs 31 11j, p<0.001), d oxygénodépendance (34.6 4.1 vs 37.8 3.7SA, p<0.0001), l âge de retour à domicile (40.5 4.5 vs 42.7 3.6SA, p<0.05) et l incidence de DBP à 36SA (30% vs 71%, p<0.0001) étaient significativement réduits dans le centre 1. A 2 ans, le score de développement ne montrait pas de différence significative entre les 2 groupes. Le traitement par HC chez des prématurés nés avant 27 SA encore intubés à J14 est associé à une diminution de la durée de VNI, d oxygénodépendance, d hospitalisation et d incidence de la DBP à 36SA sans effet neurologique néfaste à 2 ansPARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

A propos du surfactant prophylactique (comparaison de pratiques et de résultats chez des enfants de 26 à 28 SA entre deux unités de réanimation néonatale)

PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Assessment of atropine-sufentanil-atracurium anaesthesia for endotracheal intubation: an observational study in very premature infants.

International audienceBACKGROUND: Premedication before neonatal intubation is heterogeneous and contentious. The combination of a short acting, rapid onset opioid with a muscle relaxant is considered suitable by many experts. The purpose of this study was to describe the tolerance and conditions of intubation following anaesthesia with atropine, sufentanil and atracurium in very premature infants. METHODS: Monocentric, prospective observational study in premature infants born before 32 weeks of gestational age, hospitalised in the NICU and requiring semi-urgent or elective intubation. Intubation conditions, heart rate, pulse oxymetry (SpO2), arterial blood pressure and transcutaneous PCO2 (TcPCO2) were collected in real time during 30 minutes following the first drug injection. Repeated physiological measurements were analysed using mixed linear models. RESULTS: Thirty five intubations were performed in 24 infants with a median post conceptional age of 27.6 weeks and a median weight of 850 g at the time of intubation. The first attempt was successful in 74% and was similar for junior (75%) and senior (74%) operators. The operator rated conditions as "excellent" or "good" in 94% of intubations. A persistent increase in TcPCO2 as compared to baseline was observed whereas other vital parameters showed no significant variations 5, 10, 15 and 30 minutes after the first drug injection. Eighteen (51%) desaturations (SpO2 less than or equal to 80% for more than 60 seconds) and 2 (6%) bradycardia (heart rate less than100 bpm for more than 60 seconds) were observed. CONCLUSION: This drug combination offers satisfactory success rate for first attempt and intubation conditions for the operator without any significant change in heart rate and blood pressure for the patient. However it is associated with frequent desaturations and a possible persistent hypercapnia. SpO2 and PCO2 can be significantly modified during neonatal intubation and should be cautiously followed in this high-risk population

Patient-Ventilator Synchrony in Extremely Premature Neonates during Non-Invasive Neurally Adjusted Ventilatory Assist or Synchronized Intermittent Positive Airway Pressure: A Randomized Crossover Pilot Trial

International audienceIntroduction: Synchronization of non-invasive ventilation is challenging in extremely premature infants. We compared patient-ventilator synchrony between non-invasive neurally adjusted ventilatory assist (NIV-NAVA) using transdiaphragmatic (Edi) catheter and synchronized intermittent positive airway pressure (SiPAP) using an abdominal trigger. Methods: This study was a monocentric, randomized, crossover trial in premature infants born before 28 weeks of gestation, aged 3 days or more, and below 32 weeks postmenstrual age. NIV-NAVA and SiPAP were applied in a random order for 2 h with analysis of data from the second hour. The primary outcome was the asynchrony index. Results: Fourteen patients were included (median [IQR] gestational age at birth 25.6 (25.3–26.4) weeks, median [IQR] birth weight 755 [680–824] g, median [IQR] postnatal age 26.5 [19.8–33.8] days). The median (IQR) asynchrony index was significantly lower in NIV-NAVA versus SiPAP (49.9% [44.1–52.6] vs. 85.8% [74.2–90.9], p &#x3c; 0.001). Ineffective efforts and auto-triggering were significantly less frequent in NIV-NAVA versus SiPAP (3.0% vs. 32.0% p &#x3c; 0.001 and 10.0% vs. 26.6%, p = 0.004, respectively). Double triggering was significantly less frequent in SiPAP versus NIV-NAVA (0.0% vs. 9.0%, p &#x3c; 0.001). No significant difference was observed for premature cycling and late cycling. Peak Edi and swing Edi were significantly lower in NIV-NAVA as compared to SiPAP (7.7 [6.1–9.9] vs. 11.0 [6.7–14.5] μV, p = 0.006; 5.4 [4.2–7.6] vs. 7.6 [4.3–10.8] μV, p = 0.007, respectively). No significant difference was observed between NIV-NAVA and SiPAP for heart rate, respiratory rate, COMFORTneo scores, apnoea, desaturations, or bradycardias. Discussion/Conclusion: NIV-NAVA markedly improves patient-ventilator synchrony as compared to SiPAP in extremely premature infants

Shielding Parenteral Nutrition Solutions From Light: A Randomized Controlled Trial

International audienceIntroduction: Oxidant stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD). Light induces peroxide generation in parenteral nutrition (PN) solutions, creating an oxidant stress. Shielding PN from light decreases its peroxide content, which has nutrition and biochemical benefits in animals and humans. This study aims at determining whether full light protection of PN decreases the rate of bronchopulmonary dysplasia and/or death in very low-birth-weight infants. Methods: Multicenter randomized controlled trial of photoprotection, using amber bags and tubing initiated during compounding of PN and maintained throughout infusion in the light-protected (LP) group. The control group (light exposed [LE]) received PN exposed to ambient light. Depending on centers, lipids were infused either separately or as all-in-one PN. Results: In total, 590 infants born <30 weeks gestational age were included. At randomization, LE and LP groups did not differ clinically except for maximal FiO(2) before 12 hours. The rate of BPD/death was not different between groups at 28 days (77% LP vs 72% LE, P = .16) or at 36 weeks corrected age (30% LP vs 27% LE, P = .55). Multivariate analysis showed no significant effect of photoprotection on BPD and/or death. The rate of BPD/death was significantly lower (odds ratio, 0.54; 95% confidence interval, 0.32-0.93; P = .02) in infants receiving all-in-one PN vs those who received lipids separately. Conclusion: This study did not show significant beneficial effects of photoprotection. Since the decreased rate of BPD/death found with all-in-one PN relates to a center-dependent variable, this warrants further investigation