Ricardo Carbajal, MD, PhD 1 , Mats Erikson, RN, PhD 2 .

1. EUROPAIN Survey(EUROpean Pain Audit In Neonates)European survey of sedation and analgesia practices for newborns admitted to intensive care unitsVersion 2 Ricardo Carbajal, MD, PhD1, Mats Erikson, RN, PhD2. 1Principal investigator, Trousseau University Hospital, Paris, France 2Principal investigator, Örebro University Hospital, Örebro, Sweden www.europainsurvey.eu This project was supported by the European Community's Seventh Framework Programme under grant agreement no. 223767

2. Participating countries

3. Background and rationale • Neonates admitted to intensive care units undergo many painful procedures • Painful procedures include, for many of the ICU neonates, a tracheal intubation and mechanical ventilation • Pain and stress induced by mechanical ventilation and repetitive procedures or painful diseases have led to the use of sedation and analgesia in some centers • The difficulty of pain measurement has probably contributed to a wide variety of neonatal sedation and analgesia practices • Secondary hypothesis: Non ventilated babies are not sedated.

4. Practices across Europe and USA • Data on sedation and analgesia practices in ventilated neonates are very rare • SOPAIN study (1995) in USA:Factors predicting the use of on-going analgesia and sedation in neonates included: mechanical ventilation, higher gestational age, and male gender • French EPIPPAIN study (2005): the rate of continuous sedation and analgesia varied among centers between 16.7% to 90.9% • To date, there are no data permitting the comparison of neonatal pain management within the European countries • The availability of these data will enable comparison of practices with state-of-the-art knowledge

5. Main objective and type of study Main objectiveTo determine the current clinical practices regarding the use of sedative and analgesic drugs for ventilated and non ventilated newborns in different countries in Europe Type of study • Epidemiological observational study • The EUROPAIN STUDY will not interfere with routine practices of participating units • No changes in diagnostic, therapeutic or any managing strategy of patients are imposed • All treatments are authorized for included neonates since this study does not include any intervention

6. Inclusion criteria • All neonates up to a corrected age of 44 weeks post conception (ventilated AND non ventilated) • Examples: • A baby of 40 weeks gestational age can be included up to 28 days (4 weeks) of post natal age • A baby of 32 weeks gestational age can be included up to 12 weeks of post natal age

7. Data collection • Duration of data collection for every infant: 28 days • Data collection stops before 28 days if the infant leaves the unit (discharge, death, transfer to another unit or hospital) • Collected Data: demographic data, modes of respiration, continuous or intermittent sedative, analgesic or neuro-blocking drugs, pain assessment and drug withdrawal practices. • Data will be entered on a secured web-based questionnaire • The electronic data collection forms will be completed by the unit nurse or physician coordinator or the person that they will designate. • For each center, the duration of the inclusion period will be one month • The date of the start of inclusion will be communicated by the Principal investigators and the NPI

8. Timeline illustrating inclusion period Timeline illustrating an example of data collection periods for three infants (black bars) No infant is included after the one-month inclusion period but can, once included, generate data for a maximum of four weeks

9. Ethical issues • The Protocol has been approved by Local Ethics committees in France and all participating countries • The French Database has been declared to Commission nationale de l’informatique et des libertés (CNIL) that is responsible for ensuring that information technology remains at the service of citizens, and does not jeopardize human identity or breach human rights, privacy or individual or public liberties • No nominal data is sent for the analysis database • The study will be registered in “Clinicaltrials”

10. Coordination of the study MONITORING PANEL (Paris) • Monitors the progress of the study • Ensures communication with all the participating units • Constituted by 2 persons working full-time during the study period in Paris • Under the responsibility of EUROPAIN STUDY principal investigators. • Monitors the start of the study in each unit • Contacts and exchanges with local coordinators • Follows the rate of inclusions and helps with difficulties that may appear Center (Unit) Coordination • Conducted by the local nurse and medical coordinator • In contact with the National Principal Investigator (NPI) for issues dealing with national coordination and with the "Monitoring Panel" for technical or conceptual issues Country Coordination • NPI ensures that the maximum of eligible units of the country participate • NPI coordinates with the principal investigators the preparation of participating units and the study period for recruiting patients

11. Organization at the unit level • A nurse and physician coordinator as well as a person to double-check (self-audit) a sample (10%) of files will be designated for each unit. • A web site www.europainsurvey.eu has been created to post educational material for the study • The website allows to download all documents necessary for the study • The nurse and physician coordinator inform the unit staff about the study • A poster presenting the study will be distributed to all centers • The medical coordinator or a person that he (she) will chose will enter the data from the patient’s file into the web-based database • The physician coordinator will report general statistics of the unit like number of beds, number of admission, year ventilator-days • Every unit will also report existing guidelines on sedation and analgesia

12. Expected results and potential implications • This study will show the rate of sedation analgesia in NICUs across Europe • This study will reveal the differences among countries concerning the type of analgesics and sedatives used for neonates admitted to intensive care units • The results of each unit will be sent to Unit coordinators as well as global results of the whole country (benchmarking) • The neonatal network created during this study as well as the dissemination of the EUROPAIN STUDY results will allow the improvement of neonatal pain management in Europe • The availability of these data will enable comparison of practices with state-of-the-art knowledge

13. Data entry • Data will be entered in a web-based database (Voozanoo tool) available at www.europainsurvey.eu • Electronic forms are available in English and in every participating country language • Data will be entered locally in each center by the medical coordinator or the person that he will choose • The verified databases will be exported to the “Monitoring Panel” in Paris • The exported databases will contain neither last name nor first name of the patients • Records are identified by an automatically generated number

14. Website: www.europainsurvey.eu • It allows access to: • the electronic form • all useful an updated information

15. Screen of data entry