Is morphine exposure associated with acute chest syndrome in children with vaso-occlusive crisis of sickle cell disease? A 6-year case-crossover study.
BACKGROUND
Recurrent painful vaso-occlusive crises (VOC) are a hallmark of sickle cell disease (SCD), and narcotic analgesics are an effective component of therapy. However, the belief that these drugs can promote development of the acute chest syndrome (ACS) may lead to undertreatment of pain.


OBJECTIVE
The aim of this study was to explore the potential association between a dose-response effect of morphine exposure and the development of ACS in children with SCD who presented with VOC.


METHODS
A retrospective, self-matched, case-crossover design was used to study data from children with SCD who were treated with continuous-drip IV morphine (initial rate of 10 mug/kg . h) for VOC and subsequently developed ACS (index hospitalization) at a tertiary pediatric hospital in Toronto, Ontario, Canada, from April 1, 2000, to March 31, 2006. So that each child could serve as his or her own control for the analysis, a comparison hospitalization for VOC was identified for each child during which ACS did not develop (reference hospitalization). We determined the cumulative dose of morphine administered before ACS development (index interval) during the index hospitalization and the cumulative amount of morphine administered during the same time interval during the reference hospitalization (reference interval).


RESULTS
Seventeen children (13 girls, 4 boys; index hospitalization: mean [SD] age, 8.9 [4.0] years; mean [SD] weight, 30.9 [15.2] kg; reference hospitalization: mean [SD] age, 8.6 [3.4] years; mean [SD] weight, 27.3 [11.2] kg) with SCD who met all inclusion criteria were identified. There was no significant difference in the cumulative morphine dose (mean [SD] amount, 1.24 [0.60] mg/kg) during the index interval compared with the amount administered during the reference interval (mean [SD] amount, 1.44 [0.84] mg/kg).


CONCLUSIONS
Among these children with SCD who presented with VOC, the administration of morphine was not found to be associated with a dose-response effect on the risk for ACS.
Finkelstein
Yaron
Y
Department of Pediatrics, The Hospital for Sick Children, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. yfinkel@yahoo.com
Schechter
Tal
T
Garcia-Bournissen
Facundo
F
Kirby
Melanie
M
Nurmohamed
Laila
L
Juurlink
David N
DN
Blanchette
Victor
V
Koren
Gideon
G
D000208:Acute Disease; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D000755:Anemia, Sickle Cell / Q000150:complications*; D002648:Child; D003251:Constriction, Pathologic / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004913:Erythrocytes, Abnormal; D005260:Female; D006760:Hospitalization; D006801:Humans; D007511:Ischemia / Q000097:blood; D008297:Male; D008833:Microcirculation; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D012120:Respiration Disorders / Q000139:chemically induced*; D012189:Retrospective Studies; D013577:Syndrome
D000701:Analgesics, Opioid; D009020:Morphine