Evaluation of Health-Related Values and Preferences of Adults Who Were Preterm Infants and Parents of Preterm Infants Concerning Use of Prophylactic Cyclooxygenase Inhibitor Drugs.

Importance: There is wide variability in the use of prophylactic cyclooxygenase inhibitor (COX-I) drugs to prevent morbidity and mortality in preterm infants. Parents of preterm infants are rarely involved in this decision-making process. Objective: To explore the health-related values and preferences of adults who were preterm infants and families of preterm infants concerning the prophylactic use of indomethacin, ibuprofen, and acetaminophen initiated within the first 24 hours after birth. Design, Setting, and Participants: This cross-sectional study used direct choice experiments conducted in 2 phases of virtual video-conferenced interviews between March 3, 2021, and February 10, 2022: (1) a pilot feasibility study and (2) a formal study of values and preferences, using a predefined convenience sample. Participants included adults born very preterm (gestational age <32 weeks) or parents of very preterm infants currently in the neonatal intensive care unit (NICU) or having graduated from the NICU in the last 5 years. Main Outcomes and Measures: Relative importance of clinical outcomes, willingness to use each of the COX-Is when presented as the only option, preference for using prophylactic hydrocortisone vs indomethacin, willingness to use any of the COX-Is when all 3 options are available, and relative importance of having family values and preferences included in decision-making. Results: Of 44 participants enrolled, 40 were included in the formal study (31 parents and 9 adults born preterm). The median gestational age of the participant or the participant's child at birth was 26.0 (IQR, 25.0-28.8) weeks. Death (median score, 100 [IQR, 100-100]) and severe intraventricular hemorrhage (IVH) (median score, 90.0 [IQR, 80.0-100]) were rated as the 2 most critical outcomes. Based on direct choice experiments, most participants were willing to consider prophylactic indomethacin (36 [90.0%]) or ibuprofen (34 [85.0%]), but not acetaminophen (4 [10.0%]) when offered as the only option. Among participants who initially chose indomethacin (n = 36), if prophylactic hydrocortisone was offered as a potential therapy with the caveat that both cannot be used simultaneously, only 12 of 36 (33.3%) preferred to remain with indomethacin. Variability in preference was noted when all 3 COX-I options were available, indomethacin (19 [47.5%]) being the most preferred option followed by ibuprofen (16 [40.0%]), while the remainder opted for no prophylaxis (5 [12.5%]). Conclusions and Relevance: The findings of this cross-sectional study of former preterm infants and parents of preterm infants suggest that there was minimal variability in how participants valued the main outcomes, with death and severe IVH being rated as the 2 most important undesirable outcomes. While indomethacin was the most preferred form of prophylaxis, variability was noted in the choice of COX-I interventions when participants were presented with the benefits and harms of each drug.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.

Effect of Fentanyl Boluses on Cerebral Oxygenation and Hemodynamics in Preterm Infants: A Prospective Observational Study.

BACKGROUND: Fentanyl is a commonly used off-label medication for pain control and sedation in preterm infants. Yet, the effect of fentanyl on cerebral hemodynamics in preterm neonates remains unexplored. OBJECTIVE: To evaluate the effect of a bolus dose of fentanyl on the regional cerebral oxygen saturation (RcSO2), cerebral fractional tissue oxygen extraction (cFTOE) and left ventricular output (LVO) as compared with pre-administration baseline in preterm infants. METHODS: This was a prospective observational study conducted in a level III Canadian NICU from September 2017 to February 2019. Preterm infants born <37 weeks of gestation and scheduled to receive a fentanyl bolus (1-2 µg/kg/dose) were eligible. Infants with major congenital anomalies, medically unstable and those who had received fentanyl in the previous 48 h were excluded. OUTCOMES: The primary outcome was the difference between RcSO2 measured 5 min prior to and RcSO2 measured at defined time points after administration of fentanyl. RESULTS: Twenty-eight infants were enrolled during the study period (median gestational age 28 weeks; interquartile range [IQR] 25-29 weeks; median birth weight 1,035 g [IQR 830-1,292 g]; median age 4 days [IQR 3-7 days]). Mean (±standard deviation) baseline RcSO2 was 73.6% (±11.8), cFTOE was 21.9 (±11.2) and LVO was 380 (±147) mL/kg/min prior to fentanyl infusion. One-way ANOVA showed no statistically significant difference between baseline and any of the post-fentanyl cerebral oxygenation, tissue oxygen extraction or cardiac output measures (p > 0.05). CONCLUSION: Administration of fentanyl bolus for procedural pain and sedation was not shown to significantly affect cerebral oxygenation, cerebral tissue oxygen extraction or cardiac output in stable preterm infants.

Empathy in paediatric intensive care nurses part 1: Behavioural and psychological correlates.

AIM: To determine if differences exist between paediatric intensive care nurses and allied health professionals in empathy, secondary trauma, burnout, pain exposure and pain ratings of self and others. Early and late career differences were also examined. BACKGROUND: Nurses are routinely exposed to patient pain expression. This work context may make them vulnerable to adverse outcomes such as desensitization to patient pain or a compromise in personal well-being. DESIGN: Cross-sectional study. METHODS: Data were collected from a convenience sample of paediatric intensive care nurses (n = 27) and allied health professionals (n = 24), from September 2014-June 2015, at a Canadian health centre. Both groups completed one demographic and three behavioural scales. Participants underwent fMRI while rating the pain of infant and adult patients in a series of video clips. Data were analyzed using parametric and non-parametric methods. fMRI results are reported in a second paper. RESULTS: Nurses were significantly more likely to be exposed to pain at work than allied health professionals and scored significantly higher on dimensions of empathy, secondary trauma and burnout. Nurses scored their own pain and the pain of infant and adult patients, higher than allied health participants. Less experienced nurses had higher secondary trauma and burnout scores than more experienced nurses. CONCLUSIONS: Paediatric intensive care work demands, such as patient pain exposure, may be associated with nurse's higher report of empathy and pain in self and others, but also with higher levels of secondary trauma and burnout, when compared with allied health professionals.

Empathy in paediatric intensive care nurses part 2: Neural correlates.

AIMS: To determine if there are brain activity differences between paediatric intensive care nurses and allied health professionals during pain intensity rating tasks and test whether these differences are related to the population observed (infant or adult) and professional experience. BACKGROUND: The underestimation of patients' pain by healthcare professionals has generally been associated with patterns of change in neural response to vicarious pain, notably reduced activation in regions associated with affective sharing and increased activation in regions associated with regulation, compared with controls. Paediatric nurses, however, have recently been found to provide higher estimates of infants' pain in comparison to allied health controls, suggesting that changes in neural response of this population might be different than other health professionals. DESIGN: Cross-sectional study. METHODS: Functional MRI data were acquired from September 2014-June 2015 and used to compare changes in brain activity in 27 female paediatric care nurses and 24 allied health professionals while rating the pain of infants and adults in a series of video clips. RESULTS: Paediatric nurses rated infant and adult pain higher than allied health professionals, but the two groups' neural response only differed during observation of infant pain; paediatric nurses mainly showed significantly less activation in the medial prefrontal cortex (linked to cognitive empathy) and in the left anterior insula and inferior frontal cortex (linked to affective sharing). CONCLUSIONS: Patterns of neural activity to vicarious pain may vary across healthcare professions and patient populations and the amount of professional experience might explain part of these differences.