continuous infusion of fentanyl in preterm on mv

Conditions: Pain; Infant, Premature, Diseases; Respiration; Insufficient or Poor, Newborn

Summary: the objective of this randomized, double-blind trial is to compare the efficacy and safety of 2 therapeutic regimens of fentanyl administration in a population of preterm newborns of ga \<= 32 weeks in mv: * group a) continuous infusion of fentanyl + open label boluses of fentanyl; * group b) continuous infusion of placebo + open label boluses of fentanyl.

the primary objective of the study is to evaluate the analgesic superiority of fentanyl given as 'continuous infusion + boluses' versus 'boluses alone' by comparing pain scores obtained by the application of validated algometric scales for chronic pain (edin - echelle douleur inconfort nouveau-nè) and acute pain (pipp- premature infant pain profile). the secondary objective of the study is to evaluate the safety equivalence of the above 2 therapeutic regimens by recording: * rate of mechanically ventilated newborns at one week of age * age at which neonates will reach total enteral feeding * age (hours) of first meconium passage * incidence of intraventricular haemorrhage (ivh), periventricular leucomalacia (pvl) or death within 28 days of life * incidence of bladder globe during the first week of life * incidence of hypotension during the first week of life 5.2.1 pain measurement: during the study phase acute pain will be measured once a day during a heel prick by a validated algometric scale for acute pain (pipp); chronic pain will be measured 3 times a day by a validated algometric scale for chronic pain (edin). inter-rater reliability has been shown acceptable for both scales (26,27). moreover, in october 2006 the coordinating center organized a theoretical and practical course on the correct application of the pipp and edin scales (26,27) for all the participating centers in order to reduce the inter-center variability in pain measurement. the edin scores will be recorded in a specific crf (crf n°1, p. 15). the pipp scores will be reported in a specific crf (crf n° 1, pp. 8-14). 5.2.2 painful procedures: the following painful procedures, as well as the action taken to reduce pain, will be recorded in the same crf (crf n° 1, pp. 8-14): * heel pricks * endotracheal aspirations * venous blood samplings * pneumothorax drainage * peripherally inserted central catheter positioning * others (specify) 5.2.3 fentanyl open label boluses administration: all the boluses of open label fentanyl administered according to the criteria reported in paragraph 6.1.1 have to be recorded in a special crf (crf n° 1, p. 7). 5.2.4 instrumental examinations: a heart ultrasound has to be obtained in all newborns in the first week of life in order to diagnose patent ductus arteriosus. brain ultrasound has to be repeated at 4, 7 days of age and then twice a month or when clinically indicated.

Eligibility criteria:
inclusion criteria: * inborn neonates * preterm neonates ≤ 32+ 6 days weeks gestation * \< 72 hours of life * newborns on mv * within 24 hours from the beginning of mv administered through an endotracheal tube * parental written informed consent for participation in the study must be obtained exclusion criteria: * evidence of severe birth asphyxia, that is an apgar score below 4 at 5 minutes of age and/or umbilical arterial ph \< 7.0 * known genetic or chromosomal disorders * severe ivh (\> grade ii according to volpe classification (30)) * need for post-operative analgesic therapy in the first week of life * participation in another clinical trial of any placebo, drug, biological, or device conducted under the provisions of a protocol

Keywords: opioids infusion mechanical ventilation