急性肾损伤中静脉注射呋塞米后尿量反应的决定因素：一项药代动力学/药效学研究
Determinants of Urinary Output Response to IV Furosemide in Acute Kidney Injury: A Pharmacokinetic/Pharmacodynamic Study.
作者信息
Silbert Benjamin I, Ho Kwok M, Lipman Jeffrey, Roberts Jason A, Corcoran Tomas B, Morgan David J, Pavey Warren, Mas Emilie, Barden Anne E, Mori Trevor A
机构信息
1Department of Intensive Care Medicine, Fiona Stanley Hospital, Murdoch, WA, Australia.2School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, WA, Australia.3Department of Intensive Care Medicine, Royal Perth Hospital, Perth, WA, Australia.4School of Population Health, University of Western Australia, Crawley, WA, Australia.5School of Veterinary and Life Sciences, Murdoch University, Murdoch, WA, Australia.6Burns, Trauma and Critical Care Research Centre, School of Medicine, University of Queensland, Brisbane, QLD, Australia.7Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.8Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.9Department of Anaesthesia and Pain Medicine, Royal Perth Hospital, Perth, WA, Australia.10Department of Anaesthesia and Pain Medicine, Fiona Stanley Hospital, Murdoch, WA, Australia.
出版信息
Crit Care Med. 2016 Oct;44(10):e923-9. doi: 10.1097/CCM.0000000000001823.
OBJECTIVES
This study assessed the determinants of urinary output response to furosemide in acute kidney injury; specifically, whether the response is related to altered pharmacokinetics or pharmacodynamics.
DESIGN
Prospective cohort.
SETTING
Tertiary ICU.
PATIENTS
Thirty critically ill patients with acute kidney injury without preexisting renal impairment or recent diuretic exposure.
INTERVENTION
A single dose of IV furosemide.
MEASUREMENTS AND MAIN RESULTS
Baseline markers of intravascular volume status were obtained prior to administering furosemide. Six-hour creatinine clearance, hourly plasma/urinary furosemide concentrations, and hourly urinary output were used to assess furosemide pharmacokinetics/pharmacodynamics parameters. Of 30 patients enrolled, 11 had stage-1 (37%), nine had stage-2 (30%), and 10 had stage-3 (33%) Acute Kidney Injury Network acute kidney injury. Seventy-three percent were septic, 47% required norepinephrine, and 53% were mechanically ventilated. Urinary output doubled in 20 patients (67%) following IV furosemide. Measured creatinine clearance was strongly associated with the amount of urinary furosemide excreted and was the only reliable predictor of the urinary output after furosemide (area under the receiver-operating-characteristic curve, 0.75; 95% CI, 0.57-0.93). In addition to an altered pharmacokinetics (p < 0.01), a reduced pharmacodynamics response to furosemide also became important when creatinine clearance was reduced to less than 40 mL/min/1.73 m (p = 0.01). Acute kidney injury staging and markers of intravascular volume, including central venous pressure, brain-natriuretic-peptide concentration, and fractional urinary sodium excretion were not predictive of urinary output response to furosemide.
CONCLUSIONS
The severity of acute kidney injury, as reflected by the measured creatinine clearance, alters both pharmacokinetics and pharmacodynamics of furosemide in acute kidney injury, and was the only reliable predictor of the urinary output response to furosemide in acute kidney injury.
目的
本研究评估急性肾损伤患者对呋塞米尿量反应的决定因素；具体而言，该反应是否与药代动力学或药效学改变有关。
设计
前瞻性队列研究。
地点
三级重症监护病房。
患者
30例急性肾损伤的危重症患者，既往无肾功能损害或近期未使用利尿剂。
干预措施
静脉注射单剂量呋塞米。
测量指标及主要结果
在给予呋塞米之前获取血管内容量状态的基线指标。采用6小时肌酐清除率、每小时血浆/尿液呋塞米浓度以及每小时尿量来评估呋塞米的药代动力学/药效学参数。入组的30例患者中，11例为1期（37%），9例为2期（30%），10例为3期（33%）急性肾损伤网络（Acute Kidney Injury Network）定义的急性肾损伤。73%的患者为脓毒症，47%的患者需要去甲肾上腺素治疗，53%的患者接受机械通气。静脉注射呋塞米后，20例患者（67%）的尿量增加了一倍。测得的肌酐清除率与呋塞米的尿排泄量密切相关，并且是呋塞米给药后尿量的唯一可靠预测指标（受试者工作特征曲线下面积，0.75；95%可信区间，0.57 - 0.93）。除药代动力学改变外（p < 0.01），当肌酐清除率降至低于40 mL/min/1.73 m²时，对呋塞米的药效学反应降低也变得很重要（p = 0.01）。急性肾损伤分期以及血管内容量指标，包括中心静脉压、脑钠肽浓度和尿钠排泄分数，均不能预测对呋塞米的尿量反应。
结论
通过测得的肌酐清除率反映的急性肾损伤严重程度，会改变急性肾损伤患者中呋塞米的药代动力学和药效学，并且是急性肾损伤患者对呋塞米尿量反应的唯一可靠预测指标。
Zotero 插件