TY - JOUR

T1 - Morphine consumption is associated with systemic inflammation in children undergoing allogeneic hematopoietic stem cell transplantation

AU - De Pietri, Silvia

AU - Nielsen, Bettina Nygaard

AU - Ifversen, Marianne

AU - Kielsen, Katrine

AU - Müller, Klaus Gottlob

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - citrulline

KW - Hematopoietic stem cell transplantation

KW - inflammation

KW - morphine

KW - mucositis

KW - opioids

KW - pain

U2 - 10.1080/08923973.2019.1590846

DO - 10.1080/08923973.2019.1590846

M3 - Journal article

C2 - 30892107

AN - SCOPUS:85063155679

VL - 41

SP - 285

EP - 291

JO - Immunopharmacology and Immunotoxicology

JF - Immunopharmacology and Immunotoxicology

SN - 0892-3973

IS - 2

ER -