Nephrology, Dialysis and Transplantation Unit, Department of Medical Sciences, City of Health and Science, CTO Hospital, University of Turin, Via G. Zuretti 29, 10126, Turin, Italy.
Regional Antidoping and Toxicology Center "Alessandro Bertinaria", Orbassano, Turin, Italy.
J Nephrol. 2018 Dec;31(6):889-897. doi: 10.1007/s40620-018-0537-8. Epub 2018 Sep 17.
This study assessed the contribution of intracorporeal (IC) and extracorporeal clearance (EC) of furosemide in patients with septic acute kidney injury (AKI), and the relationship between plasma concentrations and urine volume.
Prospective cohort observational study of 15 patients with septic AKI undergoing continuous veno-venous hemodiafiltration (CVVHDF) divided according to urine volume (< 500 ml/12 h, Oliguria group, n = 5; > 500 ml/12 h, Diuresis group, n = 10) during continuous infusion of furosemide (120 mg/12 h) at steady-state condition. Plasma and effluent furosemide concentrations were determined by high-performance liquid chromatography (HPLC)-mass spectrometry every 12 h for 48 h.
Furosemide plasma concentrations and total body clearance (TBC) were 6.14 mg/l and 22.1 ml/min for the Oliguria group, and 2.63 mg/l and 54.4 ml/min for the Diuresis group, respectively (p < 0.05). When urine volume was < 500 ml/24 h, the furosemide plasma concentrations peaked at the potentially toxic value of 13.0 mg/l. Furosemide EC was not relevant for the Diuresis group, but it represented 18% of TBC for the Oliguria group. Furosemide plasma concentrations correlated positively with dose infusion for both groups (r = 0.728 and 0.685, p < 0.05), and negatively with urine volume only for the Diuresis (r = - 0.578, p < 0.01) but not for the Oliguria group (r = - 0.089, p = 0.715).
For patients with urine volume > 500 ml/12 h continuous infusion of furosemide up to 480 mg/24 h leads to increasing urine volume, which can predict furosemide plasma levels within its safety range. When the urine volume is lower, the furosemide plasma levels are increased beyond any further diuretic efficacy.
本研究评估了呋塞米在脓毒症急性肾损伤（AKI）患者体内的腔内（IC）和腔外（EC）清除率，并探讨了其与血浆浓度和尿量之间的关系。
前瞻性队列观察性研究，纳入 15 例接受连续静脉-静脉血液透析滤过（CVVHDF）的脓毒症 AKI 患者，根据 12 小时尿量（<500ml/12h，少尿组，n=5；>500ml/12h，利尿组，n=10）分为两组，在稳态条件下持续输注呋塞米（120mg/12h）。每隔 12 小时用高效液相色谱-质谱法（HPLC-MS）测定血浆和流出液中呋塞米的浓度，共 48 小时。
少尿组的呋塞米血浆浓度和总清除率（TBC）分别为 6.14mg/L 和 22.1ml/min，利尿组分别为 2.63mg/L 和 54.4ml/min（p<0.05）。当 24 小时尿量<500ml 时，呋塞米的血浆浓度达到潜在毒性值 13.0mg/L。呋塞米的 EC 与利尿组无关，但占少尿组 TBC 的 18%。呋塞米的血浆浓度与两组的剂量输注呈正相关（r=0.728 和 0.685，p<0.05），仅与利尿组的尿量呈负相关（r=-0.578，p<0.01），与少尿组无相关性（r=-0.089，p=0.715）。
对于尿量>500ml/12h 的患者，持续输注 480mg/24h 的呋塞米可增加尿量，这可预测呋塞米在安全范围内的血浆水平。当尿量较低时，呋塞米的血浆水平会升高，而利尿效果不再增加。
