title: Association of systolic blood pressure drop with intravenous administration of itraconazole in children with hemato-oncologic disease.
abstract: OBJECTIVE
  Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.
  
  
  METHODS
  We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP) measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥ 20%) drops.
  
  
  RESULTS
  Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0-160.33 mmHg] versus 105 [59.8-148.3 mmHg]; P<0.001). The decrease in SBP was associated with the application of continuous renal replacement therapy (CRRT) (P=0.012) and the use of inotropic (P=0.005) and hypotensive drugs (P=0.021). A clinically meaningful SBP drop was seen in 5.37% (141 out of 2,627) of the administrations, and the use of inotropics (odds ratio [OR] 6.70, 95% confidence interval [CI] 3.22-13.92; P<0.001), reducing the dose of inotropics (OR 8.08; 95% CI 1.39-46.94; P=0.02), CRRT (OR 3.10, 95% CI 1.41-6.81; P=0.005), and bacteremia (OR 2.70, 95% CI 1.32-5.51; P=0.007) were risk factors, while age was a protective factor (OR 0.93, 95% CI 0.89-0.97; P<0.001).
  
  
  CONCLUSIONS
  A decrease in SBP was associated with IV administration of itraconazole. It was particularly significant in younger patients with bacteremia using inotropic agents and during application of CRRT. Careful attention to hypotension is warranted during IV administration of itraconazole in this group of patients.
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyeong Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Pediatric Intensive Care, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Bongjin
authors.initials: B
authors.lastname: Lee
authors.affiliation: Division of Pediatric Intensive Care, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: June Dong
authors.initials: JD
authors.lastname: Park
authors.affiliation: Division of Pediatric Intensive Care, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Jeong
authors.affiliation: Division of Pediatric Intensive Care, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Yu Hyeon
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Ju
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Che Ry
authors.initials: CR
authors.lastname: Hong
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyery
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Pulmonology, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Dong In
authors.initials: DI
authors.lastname: Suh
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Kyung Duk
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Hyo Seop
authors.initials: HS
authors.lastname: Ahn
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000367:Age Factors; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D015994:Incidence; D007223:Infant; D017964:Itraconazole / Q000008:administration & dosage / Q000009:adverse effects*; D016014:Linear Models; D008297:Male; D009181:Mycoses / Q000175:diagnosis / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D016017:Odds Ratio; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole
keywords: CRRT; blood pressure; hemato-oncologic disease; hypotensive drug; inotropics; itraconazole