Lee Hyeong Jin, Lee Bongjin, Park June Dong, Jeong Hyung Joo, Choi Yu Hyeon, Ju Hee Young, Hong Che Ry, Lee Ji Won, Kim Hyery, Suh Dong In, Park Kyung Duk, Kang Hyoung Jin, Shin Hee Young, Ahn Hyo Seop
Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
Division of Pediatric Intensive Care, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea.
Drug Des Devel Ther. 2015 Dec 17;9:6489-95. doi: 10.2147/DDDT.S95218. eCollection 2015.
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.
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.
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).
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.
尽管伊曲康唑作为一种广泛用于治疗发热性中性粒细胞减少症的抗真菌药物,报告的不良反应较少,但我们发现静脉注射(IV)伊曲康唑与严重的血压(BP)下降病例有关。因此,我们评估了静脉给药期间血压下降的发生率和危险因素。
我们回顾了2012年1月至2013年12月接受静脉伊曲康唑治疗的血液肿瘤疾病患儿的病历。通过分析伊曲康唑给药前4小时至给药后4小时的收缩压(SBP)测量值,我们评估了SBP的变化以及SBP下降的危险因素,尤其是具有临床意义(≥20%)的下降。
伊曲康唑共对180例患者给药2627次。伊曲康唑给药后4小时的SBP低于给药前4小时(104[53.0-160.33 mmHg]对105[59.8-148.3 mmHg];P<0.001)。SBP的下降与持续肾脏替代治疗(CRRT)的应用(P=0.012)、使用血管活性药物(P=0.005)和降压药物(P=0.021)有关。在5.37%(2627次给药中的141次)的给药中观察到具有临床意义的SBP下降,使用血管活性药物(比值比[OR]6.70,95%置信区间[CI]3.22-13.92;P<0.001)、减少血管活性药物剂量(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)和菌血症(OR 2.70,95%CI 1.32-5.51;P=0.007)是危险因素,而年龄是保护因素(OR 0.93,95%CI 0.89-0.97;P<0.001)。
SBP下降与静脉注射伊曲康唑有关。在使用血管活性药物的菌血症年轻患者以及CRRT应用期间尤为显著。在这组患者静脉注射伊曲康唑期间,有必要密切关注低血压情况。