Sedation/analgesia practices in neonatal intensive care units: Results from the prospective observational EUROPAIN study

Background Neonates undergoing pain/stress during ICU care frequently receive sedation/analgesia. We determined the current use of sedation/analgesia in 243 European NICUs from 18 countries. Comparative effectiveness research on these practices and the factors associated with them will allow definition of best practices and future clinical trials. Methods EUROPAIN (EUROpean-Pain-Audit-In-Neonates) is a prospective observational study of sedation/analgesia management in NICU patients. All neonates admitted to NICUs over a 1month period were included. Data on demographics, modes of respiration, use of continuous or intermittent sedation/analgesia drugs or neuromuscular blockers, pain assessments and drug withdrawal syndromes were collected prospectively during the first 28 days of NICU hospitalization. Multivariable linear regression models and propensity scores were used to assess the association between duration of tracheal ventilation (DTV) and exposure to opioids, and/or sedatives-hypnotics and/or general anesthetics (O-SH-GA). This study is registered at ClinicalTrials.gov (#NCT01694745). Findings A total of 6680 neonates were enrolled with a median (IQR) gestational age of 35.6 (32.039.0) weeks gestation, and a birth weight of 2370 (1570-3170) grams. Among the 6680 neonates, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV), and 3042 spontaneous ventilation (SV). 2294 (34.3%) infants received sedation/analgesia in continuous infusion, intermittent doses or both, comprising 81.5%, 17.8%, and 9.3% of the TV, NIV, and SV groups, respectively (p<0.0001). In participating NICUs, 89.3% (70-100% [median rate; IQR]) of TV neonates received sedation/analgesia. Opioids were given to 1764/6680 (26.4%) and to 1589/2142 (74.2%) in all neonates and in the TV group, respectively. Corresponding figures for midazolam were 576/6680 (8.6%) and 536/2142 (25.0%). 542/2142 (25.3%) neonates in the TV group received neuromuscular blockers including 146 (6.8%) who received them in continuous infusions. Pain assessments were recorded in 58.5%, 45.0% and 30.4% of neonates in the TV, NIV, and SV groups, respectively (p<0.0001). Among TV neonates, those receiving O-SH-GA required longer DTV (136.2 [173.1] hours) compared to those who did not (39.8 [94.7] hours), p<0.0001. Interpretation Three-fourths of TV neonates receive opioids and one-fourth receive midazolam. Wide variations in sedation/analgesia practices occur among NICUs and countries. Widespread use of O-SH-GA among intubated neonates may possibly prolong their need for mechanical ventilation but further research is needed. Funding The European Community's Seventh Framework Programme under grant agreement no.