Respiratory outcomes and survival after unplanned extubation in the NICU: a prospective cohort study from the SEPREVEN trial.

OBJECTIVE: To compare reintubation rates after planned extubation and unplanned extubation (UE) in patients in neonatal intensive care units (NICUs), to analyse risk factors for reintubation after UE and to compare outcomes in patients with and without UE. DESIGN: Prospective, observational study nested in a randomised controlled trial (SEPREVEN/Study on Epidemiology and PRevention of adverse EVEnts in Neonates). Outcomes were expected to be independent of the intervention tested. SETTING: 12 NICUs in France with a 20-month follow-up, starting November 2015. PATIENTS: n=2280 patients with a NICU stay >2 days, postmenstrual age ≤42 weeks on admission. INTERVENTIONS/EXPOSURE: Characteristics of UE (context, timing, sedative administration in the preceding 6 hours, weaning from ventilation at time of UE) and patients. MAIN OUTCOME MEASURES: Healthcare professional-reported UE rates, reintubation/timing after extubation, duration of mechanical ventilation, mortality and bronchopulmonary dysplasia (BPD). RESULTS: There were 162 episodes of UE (139 patients, median gestational age (IQR) 27.3 (25.6-31.7) weeks). Cumulative reintubation rates within 24 hours and 7 days of UE were, respectively, 50.0% and 57.5%, compared with 5.5% and 12.3% after a planned extubation. Independent risk factors for reintubation within 7 days included absence of weaning at the time of UE (HR, 95% CI) and sedatives in the preceding 6 hours (HR 1.93, 95% CI 1.04 to 3.60). Mortality at discharge did not differ between patients with planned extubation or UE. UE was associated with a higher risk of BPD. CONCLUSION: In the SEPREVEN trial, reintubation followed UE in 58% of the cases, compared with 12% after planned extubation. TRIAL REGISTRATION NUMBER: NCT02598609.

Error disclosure in neonatal intensive care: a multicentre, prospective, observational study.

IMPORTANCE: Surveys based on hypothetical situations suggest that health-care providers agree that disclosure of errors and adverse events to patients and families is a professional obligation but do not always disclose them. Disclosure rates and reasons for the choice have not previously been studied. OBJECTIVE: To measure the proportion of errors disclosed by neonatal intensive care unit (NICU) professionals to parents and identify motives for and barriers to disclosure. DESIGN: Prospective, observational study nested in a randomised controlled trial (Study on Preventing Adverse Events in Neonates (SEPREVEN); ClinicalTrials.gov). Event disclosure was not intended to be related to the intervention tested. SETTING: 10 NICUs in France with a 20-month follow-up, starting November 2015. PARTICIPANTS: n=1019 patients with NICU stay ≥2 days with ≥1 error. EXPOSURE: Characteristics of errors (type, severity, timing of discovery), patients and professionals, self-reported motives for disclosure and non-disclosure. MAIN OUTCOME AND MEASURES: Rate of error disclosure reported anonymously and voluntarily by physicians and nurses; perceived parental reaction to disclosure. RESULTS: Among 1822 errors concerning 1019 patients (mean gestational age: 30.8±4.5 weeks), 752 (41.3%) were disclosed. Independent risk factors for non-disclosure were nighttime discovery of error (OR 2.40; 95% CI 1.75 to 3.30), milder consequence (for moderate consequence: OR 1.85; 95% CI 0.89 to 3.86; no consequence: OR 6.49; 95% CI 2.99 to 14.11), a shorter interval between admission and error, error type and fewer beds. The most frequent reported reasons for non-disclosure were parental absence at its discovery and a perceived lack of serious consequence. CONCLUSION AND RELEVANCE: In the particular context of the SEPREVEN randomised controlled trial of NICUs, staff did not disclose the majority of errors to parents, especially in the absence of moderate consequence for the infant. TRIAL REGISTRATION NUMBER: NCT02598609.

Study on preventing adverse events in neonates (SEPREVEN): A stepped-wedge randomised controlled trial to reduce adverse event rates in the NICU.

INTRODUCTION: Adverse events (AE) in care are recognized as a leading cause of mortality and injury in patients. Improving patients' safety is difficult to achieve. Therefore, innovative research strategies are needed to identify errors in subgroups of patients and related severity of outcomes as well as reliably measured efficiency of reproducible strategies to improve safety. This trial aims to evaluate the impact of a combined multiprofessional education program on the rate of AE in neonatal intensive care units (NICUs). METHODS AND ANALYSIS: This is a stepped-wedge cluster randomised controlled trial with 3 clusters each containing 4 units. The study time period will be 20 months. The education program will be implemented within each cluster following a random sequence with a control period, a 4-month transition period and a post-educational intervention period. Eligibility criteria: for clusters: 6 NICUs from Ile-de-France and 6 NICUs from different regions in France; for patients: in-hospital during the study period (November 23, 2015 and November 2, 2017 [inclusion start dates varying by unit]) in one of the 12 NICUs; corrected gestational age ≤42 weeks upon admission; hospitalization period >2 days; and parents informed and not opposed to the use of their newborn's data. A routine occurrence reporting of medical errors and their consequence will take place during the entire study period. The intervention will combine an education to implement a standardized root cause analysis method, creation of bundles (insertion, daily goals, maintenance bundles) to prevent catheter-associated blood-stream infection and a poster to prevent extravasation injuries. OUTCOME: We hypothesize a reduction from 60 (control) to 50 (intervention) AE/1000 patient-days. The primary outcome will be the rate of AE/1000 patient-days in the NICU. TRIAL REGISTRATION NUMBER: NCT02598609, trial registered November 6, 2015. https://clinicaltrials.gov/ct2/show/NCT02598609. ETHICS AND DISSEMINATION: Study approved by the regional ethic committee CPP Ile-de-France III (no 2014-A01751-46). The results will be published in peer-reviewed journals.

Targeting p16INK4a Promotes Lipofibroblasts and Alveolar Regeneration after Early-Life Injury.

Rationale: Promoting endogenous pulmonary regeneration is crucial after damage to restore normal lungs and prevent the onset of chronic adult lung diseases.Objectives: To investigate whether the cell-cycle inhibitor p16INK4a limits lung regeneration after newborn bronchopulmonary dysplasia (BPD), a condition characterized by the arrest of alveolar development, leading to adult sequelae.Methods: We exposed p16INK4a-/- and p16INK4aATTAC (apoptosis through targeted activation of caspase 8) transgenic mice to postnatal hyperoxia, followed by pneumonectomy of the p16INK4a-/- mice. We measured p16INK4a in blood mononuclear cells of preterm newborns, 7- to 15-year-old survivors of BPD, and the lungs of patients with BPD.Measurements and Main Results: p16INK4a concentrations increased in lung fibroblasts after hyperoxia-induced BPD in mice and persisted into adulthood. p16INK4a deficiency did not protect against hyperoxic lesions in newborn pups but promoted restoration of the lung architecture by adulthood. Curative clearance of p16INK4a-positive cells once hyperoxic lung lesions were established restored normal lungs by adulthood. p16INK4a deficiency increased neutral lipid synthesis and promoted lipofibroblast and alveolar type 2 (AT2) cell development within the stem-cell niche. Besides, lipofibroblasts support self-renewal of AT2 cells into alveolospheres. Induction with a PPARγ (peroxisome proliferator-activated receptor γ) agonist after hyperoxia also increased lipofibroblast and AT2 cell numbers and restored alveolar architecture in hyperoxia-exposed mice. After pneumonectomy, p16INK4a deficiency again led to an increase in lipofibroblast and AT2 cell numbers in the contralateral lung. Finally, we observed p16INK4a mRNA overexpression in the blood and lungs of preterm newborns, which persisted in the blood of older survivors of BPD.Conclusions: These data demonstrate the potential of targeting p16INK4a and promoting lipofibroblast development to stimulate alveolar regeneration from childhood to adulthood.

Characteristics of prescription in 29 Level 3 Neonatal Wards over a 2-year period (2017-2018). An inventory for future research.

OBJECTIVES: The primary objective of this study is to determine the current level of patient medication exposure in Level 3 Neonatal Wards (L3NW). The secondary objective is to evaluate in the first month of life the rate of medication prescription not cited in the Summary of Product Characteristics (SmPC). A database containing all the medication prescriptions is collected as part of a prescription benchmarking program in the L3NW. MATERIAL AND METHODS: The research is a two-year observational cohort study (2017-2018) with retrospective analysis of medications prescribed in 29 French L3NW. Seventeen L3NW are present since the beginning of the study and 12 have been progressively included. All neonatal units used the same computerized system of prescription, and all prescription data were completely de-identified within each hospital before being stored in a common data warehouse. RESULTS: The study population includes 27,382 newborns. Two hundred and sixty-one different medications (International Nonproprietary Names, INN) were prescribed. Twelve INN (including paracetamol) were prescribed for at least 10% of patients, 55 for less than 10% but at least 1% and 194 to less than 1%. The lowest gestational ages (GA) were exposed to the greatest number of medications (18.0 below 28 weeks of gestation (WG) to 4.1 above 36 WG) (p<0.0001). In addition, 69.2% of the 351 different combinations of an medication INN and a route of administration have no indication for the first month of life according to the French SmPC. Ninety-five percent of premature infants with GA less than 32 weeks received at least one medication not cited in SmPC. CONCLUSION: Neonates remain therapeutic orphans. The consequences of polypharmacy in L3NW should be quickly assessed, especially in the most immature infants.

Continuous intravenous to oral morphine switch in very premature ventilated infants: A retrospective study on efficacy, efficiency, and tolerability.

Background: Continuous intravenous (IV) morphine is commonly used in ventilated neonates. Oral route is theoretically feasible but data on oral morphine in ventilated premature infants are lacking. Objective: To assess the efficacy, efficiency, and tolerability of a continuous intravenous to oral morphine switch protocol. Design: Retrospective study. Setting: Single level III center's neonatal intensive care unit. Patients: Ventilated premature infants hospitalized in the NICU in 2016 and 2017, receiving continuous IV morphine with an expected ventilation course of at least 72 more hours. We excluded patients treated for withdrawal syndrome or palliative care. Interventions: Continuous IV to oral morphine switch with the same initial cumulated daily dose. Main outcome measures: Pain scores (ComfortNeo scale) and morphine doses were analyzed over time using Friedman's test in the 24 hours preceding and the 48 hours following the oral switch. Adverse effects attributable to opioids were collected. Results: Seventeen infants were included with a median [IQR] gestational age at birth of 25.9 [24.6-26.9] weeks and a median postnatal age at oral switch of 30 [22-36] days. One patient's intravenous treatment had to be resumed because of a high ComfortNeo score. All others remained on oral morphine. No significant change over time was observed for ComfortNeo scores (P = .15). Median [IQR] doses were 13.5 [10-20] µg/kg/h in the IV period and significantly increased to 15 [10-25] µg/kg/h in the oral period (P = .009). No short-term respiratory, digestive, or urinary adverse event was observed. After a median [IQR] duration of 13 [4-20] days of oral morphine treatment, 11 (65%) patients showed signs of withdrawal. Upon hospital discharge, 16 infants (94%) had bronchopulmonary dysplasia and none had severe cerebral abnormality on brain imaging. Conclusion: Oral morphine might be useful in ventilated neonates in the NICU but deserves further studies and additional safety assessment.

Apology in cases of medical error disclosure: Thoughts based on a preliminary study.

BACKGROUND: Disclosing medical errors is considered necessary by patients, ethicists, and health care professionals. Literature insists on the framing of this disclosure and describes the apology as appropriate and necessary. However, this policy seems difficult to put into practice. Few works have explored the function and meaning of the apology. OBJECTIVE: The aim of this study was to explore the role ascribed to apology in communication between healthcare professionals and patients when disclosing a medical error, and to discuss these findings using a linguistic and philosophical perspective. METHODS: Qualitative exploratory study, based on face-to-face semi-structured interviews, with seven physicians in a neonatal unit in France. Discourse analysis. RESULTS: Four themes emerged. Difference between apology in everyday life and in the medical encounter; place of the apology in the process of disclosure together with explanations, regrets, empathy and ways to avoid repeating the error; effects of the apology were to allow the patient-physician relationship undermined by the error, to be maintained, responsibility to be accepted, the first steps towards forgiveness to be taken, and a less hierarchical doctor-patient relationship to be created; ways of expressing apology ("I am sorry") reflected regrets and empathy more than an explicit apology. CONCLUSION: This study highlights how the act of apology can be seen as a "language act" as described by philosophers Austin and Searle, and how it functions as a technique for making amends following a wrongdoing and as an action undertaken in order that neither party should lose face, thus echoing the sociologist Goffmann's interaction theory. This interpretation also accords with the views of Lazare, for whom the function of apology is a restoration of dignity after the humiliation of the error. This approach to the apology illustrates how meaning and impact of real-life language acts can be clarified by philosophical and sociological ideas.

Delivery room deaths of extremely preterm babies: an observational study.

OBJECTIVE: Many extremely preterm neonates die in the delivery room (DR) after decisions to withhold or withdraw life-sustaining treatments or after failed resuscitation. Specific palliative care is then recommended but sparse data exist about the actual management of these dying babies. The objective of this study was to describe the clinical course and management of neonates born between 22 and 26 weeks of gestation who died in the DR in France. DESIGN, SETTING, PATIENTS: Prospective study including neonates, who were liveborn between 22+0 and 26+6 weeks of gestation and died in the DR in 2011, among infants included in the EPIPAGE-2 study at the 18 centres participating in this substudy of extremely preterm neonates. Data were collected by a questionnaire completed by the professional caring for each baby. RESULTS: The study included 73 children, with a median (IQR) gestational age of 24 (23-24) weeks. Median (IQR) duration of life was 53 (20-82) min. All but one were both wrapped and warmed. Pain was assessed for 72%, although without using any scale. Gasping was described for 66%. Comfort medications were administered to 35 children (50%), significantly more frequently to babies with gasping (p=0.001). Mother-child contact was reported for 78%, and psychological support offered to parents of 92%. CONCLUSIONS: Non-pharmacological comfort care and parental support were routinely given. Comfort medication was given much more frequently than previously reported in other DRs. These data should encourage work on the indications for comfort medication and the interpretation of gasping.

Surgical necrotizing enterocolitis: are intestinal lesions more severe in infants with low birth weight?

PURPOSE: This study examines whether the intestinal lesions of necrotizing enterocolitis (NEC) in infants undergoing surgery are more severe in patients with extremely low birth weight (BW). METHODS: Between 1980 and 2000, 128 infants underwent laparotomy for NEC: 90 in the acute phase, and 38 for secondary stenosis. Resections were limited to areas of transparietal bowel necrosis and to secondary stenoses. The authors studied the extent of initial bowel lesions at initial laparotomy, and, in the survivors, the extent of bowel resections and the existence of digestive sequelae, with a median follow-up of 24 (range, 1 to 247) months. Children with BW < or =1,000 g (group 1, 22 patients) and greater than 1,000 g (group 2, 103 patients) were compared by using chi(2) and t test. RESULTS: Patients' survival rate was 87%: 68% and 91% in the groups 1 and 2, respectively (P =.01). No significant difference between the 2 groups was seen: (1) for the rate of patients with panintestinal lesions at initial surgery (12%); (2) in the survivors, the ratio of remaining to total length of jejuno-ileum (mean 88%), the number of colonic segments resected (mean 1.2), the rate of survivors without distal ileum (34%), ileo-caecal valve (39%), or right colon (29%); and (3) for the existence of digestive symptoms, even minor, at last follow-up (25%). CONCLUSIONS: Although the prognosis of surgical NEC was worse in infants with extremely low birth weight, the intestinal lesions were not found more severe in these patients.