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Updated: Jan 27, 2026
Isolation and Transplantation of Hematopoietic Stem Cells HSCs
Published on: February 25, 2007
Morphine consumption is associated with systemic inflammation in children undergoing allogeneic hematopoietic stem
Silvia De Pietri1, Bettina Nygaard Nielsen2, Marianne Ifversen1
1a Department of Pediatrics and Adolescent Medicine , Copenhagen University Hospital, Rigshospitalet , Copenhagen , Denmark.
Insights
Opioid use in children after stem cell transplants is linked to systemic inflammation, not gut damage. Understanding this helps improve pain management for pediatric patients undergoing hematopoietic stem cell transplantation (HSCT).
Area of Science:
- Pediatric Hematology/Oncology
- Pain Management
- Gastrointestinal Toxicity
Background:
- Allogeneic hematopoietic stem cell transplantation (HSCT) frequently causes severe pain in children due to chemotherapy-induced gastrointestinal toxicity.
- Individual variations in pain perception and opioid requirements post-HSCT are not well understood, hindering personalized pain management.
- Investigating the relationship between opioid consumption and biomarkers of toxicity and inflammation is crucial for optimizing care.
Purpose of the Study:
- To examine the association between opioid consumption and markers of gastrointestinal toxicity (plasma citrulline) and systemic inflammation (plasma C-reactive protein [CRP] and interleukin-6 [IL-6]).
- To explore factors influencing pain and opioid needs in children undergoing HSCT.
Main Methods:
- Retrospective analysis of 38 children undergoing HSCT in Denmark (2010-2012).
- Opioid doses recorded as intravenous morphine equivalents (MEs) on days 0-21 post-HSCT.
- Daily CRP measurements (days 0-21), day 7 IL-6, and pre-conditioning, day 7, and day 21 citrulline measurements.
Main Results:
- Nearly all children (97%) received opioids during the study period.
- C-reactive protein (CRP) levels and opioid doses peaked around days 9-10, while plasma citrulline (a marker of enterocyte loss) reached its lowest point on day 7.
- Higher CRP levels significantly correlated with increased opioid consumption (ME dose), as did IL-6 levels on day 7. Plasma citrulline showed no correlation with opioid use.
Conclusions:
- Opioid consumption in the early phase after HSCT is primarily associated with systemic inflammation, not the degree of gastrointestinal enterocyte loss.
- These findings enhance the understanding of mucositis-related pain mechanisms in pediatric HSCT.
- The results may inform future therapeutic strategies for managing pain in these vulnerable patients.
Abstract:
Background: The majority of children undergoing allogenic hematopoietic stem cell transplantation (HSCT) experience severe pain due to chemotherapy-induced gastrointestinal toxicity. Inter-individual differences in pain perceived and opioid consumption remain unexplained, limiting the possibility for individualized pain control. The aim of this study was to investigate the associations between opioid consumption and markers of gastrointestinal toxicity (plasma citrulline) and systemic inflammation (plasma CRP and IL-6) in these patients. Methods: We retrospectively included 38 children undergoing HSCT in Denmark in 2010-2012. Opioids doses on days 0-21 post-HSCT were registered as intravenous morphine equivalents (MEs). CRP was measured daily on days 0-21. IL-6 was measured on day 7. Citrulline was measured before conditioning, on days 7 and 21. Results: Out of 38 children, 37 (97%) received opioids during days 0-21. CRP level and ME dose peaked on days 9-10 while citrulline level reached a nadir on day 7 indicating maximum enterocyte loss. CRP was associated with ME dose, with an estimated increase of 0.030 mg/kg (95% CI 0.024-0.035) in ME for a 50% increase in CRP level on the same day (p < .001). IL-6 was correlated with ME on day 7 (rho = 0.55, p = .002). Citrulline did not correlate with ME. Conclusions: Opioid consumption in the early post-HSCT period is associated with the degree of chemotherapy-induced systemic inflammation and not with the extent of enterocyte loss. These findings contribute to our understanding of mucositis-related pain and may be of interest for future studies on therapeutic strategies.
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