PEDIATRICS Vol. 115 No. 5 May 2005, pp. 1351-1359 (doi:10.1542/10.1542/peds.2004-1398)
Morphine, Hypotension, and Adverse Outcomes Among Preterm Neonates: Who’s to Blame? Secondary Results From the NEOPAIN Trial
,||,¶
* Department of Pediatrics
Department of Anesthesiology
|| Department of Neurobiology
¶ Department of Pharmacology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Maryland Medical Research Institute, Baltimore, Maryland
Objectives. Hypotension occurs commonly among preterm neonates, but its cause and consequences remain unclear. Secondary data analyses from the NEOPAIN trial identified the clinical factors associated with hypotension and examined the contributions of morphine treatment or hypotension to severe intraventricular hemorrhage (IVH) (grades 3 and 4), any IVH (grades 1–4), or death.
Methods. In the NEOPAIN trial, 898 ventilated neonates between 23 and 32 weeks of gestation were enrolled, with equal numbers randomized to receive masked morphine or placebo infusions. Additional doses of open-label morphine were administered as necessary by medical staff members. IVH was diagnosed with centralized readings of early and late cranial ultrasonograms. Hypotension was assessed before study drug infusion, during the loading dose, and at 24 and 72 hours during study drug infusion. Logistic regression analyses with stepdown elimination identified the predictor factors associated with the hypotension, severe IVH, any IVH, or death outcomes at each time point.
Results. Hypotension was associated with 23 to 26 weeks of gestation, morphine infusions, severity of illness, additional morphine doses, and prior hypotension. Severe IVH was associated with shorter gestation, higher Clinical Risk Index for Babies scores, no prenatal steroids, pulmonary hemorrhage, hypotension before the loading dose, and morphine doses before intubation and at 25 to 72 hours. Neonatal deaths were associated with 23 to 26 weeks of gestation, higher Clinical Risk Index for Babies scores, pulmonary hemorrhage, patent ductus arteriosus, thrombocytopenia, and hypotension before the loading dose. Morphine infusions were not a significant factor in logistic models for severe IVH, any IVH, or death.
Conclusions. Preemptive morphine infusions, additional morphine, and lower gestational age were associated with hypotension among preterm neonates. Severe IVH, any IVH, and death were associated with preexisting hypotension, but morphine therapy did not contribute to these outcomes. Morphine infusions, although they cause hypotension, can be used safely for most preterm neonates but should be used cautiously for 23- to 26-week neonates and those with preexisting hypotension.
Key Words: morphine • hypotension • preterm neonates • outcomes • pain • intraventricular hemorrhage • drug toxicity
Abbreviations: IVH, intraventricular hemorrhage • PVL, periventricular leukomalacia • OR, odds ratio • CI, confidence interval • CRIB, Clinical Risk Index for Babies • BP, blood pressure • SGA, small for gestational age
Accepted Jan 4, 2005.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  K. J. S. Anand, B. J. Anderson, N. H. G. Holford, R. W. Hall, T. Young, B. Shephard, N. S. Desai, B. A. Barton, and for the NEOPAIN Trial Investigators Group Morphine pharmacokinetics and pharmacodynamics in preterm and term neonates: secondary results from the NEOPAIN trial Br. J. Anaesth., November 1, 2008; 101(5): 680 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-C. Roze, S. Denizot, R. Carbajal, P.-Y. Ancel, M. Kaminski, C. Arnaud, P. Truffert, S. Marret, J. Matis, G. Thiriez, et al. Prolonged Sedation and/or Analgesia and 5-Year Neurodevelopment Outcome in Very Preterm Infants: Results From the EPIPAGE Cohort Arch Pediatr Adolesc Med, August 1, 2008; 162(8): 728 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Roka, K. T. Melinda, B. Vasarhelyi, T. Machay, D. Azzopardi, and M. Szabo Elevated Morphine Concentrations in Neonates Treated With Morphine and Prolonged Hypothermia for Hypoxic Ischemic Encephalopathy Pediatrics, April 1, 2008; 121(4): e844 - e849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Roberts, T. A. Leone, W. H. Edwards, W. D. Rich, and N. N. Finer Premedication for Nonemergent Neonatal Intubations: A Randomized, Controlled Trial Comparing Atropine and Fentanyl to Atropine, Fentanyl, and Mivacurium Pediatrics, October 1, 2006; 118(4): 1583 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Finer, R. J. Powers, C.-h. S. Ou, D. Durand, D. Wirtschafter, J. B. Gould, and for the California Perinatal Quality Care Collabor Prospective Evaluation of Postnatal Steroid Administration: A 1-Year Experience From the California Perinatal Quality Care Collaborative Pediatrics, March 1, 2006; 117(3): 704 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.J.S. Anand and R. W. Hall Morphine, Hypotension, and Intraventricular Hemorrhage Pediatrics, January 1, 2006; 117(1): 250 - 252. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Perlman Morphine, Hypotension, and Intraventricular Hemorrhage: In Reply Pediatrics, January 1, 2006; 117(1): 252 - 253. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Perlman Morphine, Hypotension, and Intraventricular Hemorrhage in the Ventilated Premature Infant Pediatrics, May 1, 2005; 115(5): 1416 - 1418. [Full Text] [PDF]
|
|
