{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:39:51Z","timestamp":1791279591201,"version":"4.1.0"},"reference-count":47,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,1]]},"abstract":"<jats:p>Background. Morphine alleviates prolonged pain, reduces behavioral and hormonal stress responses induced by surgery among term neonates, and improves ventilator synchrony and sedation among ventilated preterm neonates, but its analgesic effects on the acute pain caused by invasive procedures remain unclear.<\/jats:p><jats:p>Objective. To investigate the analgesic efficacy of intravenously administered morphine on heel stick-induced acute pain among preterm neonates.<\/jats:p><jats:p>Design. This study was nested within a prospective, randomized, double-blind, multicenter, placebo-controlled trial (the NEOPAIN Trial).<\/jats:p><jats:p>Setting. A tertiary-care NICU in a teaching hospital.<\/jats:p><jats:p>Participants. Forty-two preterm neonates undergoing ventilation.<\/jats:p><jats:p>Interventions. Neonates were randomized to either the morphine (loading dose of 100 \u03bcg\/kg, followed by infusions of 10\u201330 \u03bcg\/kg per hour according to gestation, N = 21) or placebo (5% dextrose infusions, N = 21) group. Pain responses to 3 heel sticks were evaluated, ie, before the loading dose (T1), 2 to 3 hours after the loading dose (T2), and 20 to 28 hours after the loading dose (T3).<\/jats:p><jats:p>Main Outcomes Measures. Pain was assessed with the Douleur Aigue\u0308 Nouveau-ne\u0301 (DAN) scale (behavioral pain scale) and the Premature Infant Pain Profile (PIPP) (multidimensional pain scale); plasma morphine levels were measured at T3.<\/jats:p><jats:p>Results. Infants in the placebo and morphine groups had similar gestational ages (mean \u00b1 SD: 27.2 \u00b1 1.7 vs 27.3 \u00b1 1.8 weeks) and birth weights (972 \u00b1 270 vs 947 \u00b1 269 g). Mean \u00b1 SD DAN pain scores at T1, T2, and T3 were 4.8 \u00b1 4.0, 4.6 \u00b1 2.9, and 4.7 \u00b1 3.6, respectively, for the placebo group and 4.5 \u00b1 3.8, 4.4 \u00b1 3.7, and 3.1 \u00b1 3.4 for the morphine group. The within-group factor (pain at T1, T2, and T3) was not statistically different over time. The between-group analysis (infants receiving placebo versus those receiving morphine) showed no significant differences. Mean \u00b1 SD PIPP pain scores at T1, T2, and T3 were 11.5 \u00b1 4.8, 11.1 \u00b1 3.7, and 9.1 \u00b1 4.0, respectively, for the placebo group and 10.0 \u00b1 3.6, 8.8 \u00b1 4.9, and 7.8 \u00b1 3.6 for the morphine group. The within-group factor was statistically different over time. The between-group analysis showed no significant differences. Mean \u00b1 SD plasma morphine levels at T3 were 0.44 \u00b1 1.79 ng\/mL and 63.36 \u00b1 33.35 ng\/mL for the placebo and morphine groups, respectively. There was no correlation between plasma morphine levels and pain scores at T3 (DAN, R = \u22120.05; PIPP, R = \u22120.02).<\/jats:p><jats:p>Conclusions. Despite its routine use in the NICU, morphine given as a loading dose followed by continuous intravenous infusions does not appear to provide adequate analgesia for the acute pain caused by invasive procedures among ventilated preterm neonates.<\/jats:p>","DOI":"10.1542\/peds.2004-1425","type":"journal-article","created":{"date-parts":[[2005,6,1]],"date-time":"2005-06-01T17:19:46Z","timestamp":1117646386000},"page":"1494-1500","source":"Crossref","is-referenced-by-count":210,"title":["Morphine Does Not Provide Adequate Analgesia for Acute Procedural Pain Among Preterm Neonates"],"prefix":"10.1542","volume":"115","author":[{"given":"Ricardo","family":"Carbajal","sequence":"first","affiliation":[{"name":"Neonatal Intensive Care Unit, Poissy Saint Germain Hospital, Poissy, France"},{"name":"Centre National de Ressources de Lutte Contre la Douleur, Ho\u0302pital d\u2019Enfants Armand Trousseau, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lenclen","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Poissy Saint Germain Hospital, Poissy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Jugie","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Poissy Saint Germain Hospital, Poissy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Paupe","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, Poissy Saint Germain Hospital, Poissy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Barton","sequence":"additional","affiliation":[{"name":"Maryland Medical Research Institute, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwaljeet J. S.","family":"Anand","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences, Arkansas Children\u2019s Hospital, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2005,6,1]]},"reference":[{"key":"2021120819240422800_R1","doi-asserted-by":"crossref","unstructured":"Johnston CC, Collinge JM, Henderson SJ, Anand KJ. A cross-sectional survey of pain and pharmacological analgesia in Canadian neonatal intensive care units. Clin J Pain.\u20081997;13:308\u2013312","DOI":"10.1097\/00002508-199712000-00008"},{"key":"2021120819240422800_R2","doi-asserted-by":"crossref","unstructured":"Simons SH, van Dijk M, Anand KS, Roofthooft D, van Lingen RA, Tibboel D. Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. 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