Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Departments of Neurology and Neurosurgery, University of North Carolina School of Medicine, Chapel Hill, NC.
Crit Care Med. 2019 Jun;47(6):800-808. doi: 10.1097/CCM.0000000000003716.
To evaluate enhanced renal clearance over time in patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage via measured creatinine clearance and to compare measured creatinine clearance to creatinine clearance calculated by the Cockcroft-Gault equation and estimated glomerular filtration rate calculated by the Modification of Diet in Renal Diseases equation.
Prospective, observational study.
Neurosciences ICU in a tertiary care academic medical center.
Study participants had an admission diagnosis of aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage, an expected neurosciences ICU length of stay greater than 48 hours, no evidence of renal dysfunction (admission serum creatinine < 1.5 mg/dL), and no history of chronic kidney disease.
Eight-hour urine collections to measure creatinine clearance were collected daily as the primary method of measuring renal function. Creatinine clearance was also calculated using the Cockcroft-Gault equation and estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Enhanced renal clearance was defined as a measured creatinine clearance greater than the calculated creatinine clearance via Cockcroft-Gault and estimated glomerular filtration rate via Modification of Diet in Renal Disease. Augmented renal clearance was defined by a measured creatinine clearance greater than or equal to 130 mL/min/1.73 m. Relevant demographic, clinical, and outcome data were recorded.
Fifty aneurysmal subarachnoid hemorrhage patients and 30 intracerebral hemorrhage patients were enrolled, contributing 590 individual measurements. Patients with aneurysmal subarachnoid hemorrhage had a higher mean measured creatinine clearance compared with the mean calculated creatinine clearance based on the Cockcroft-Gault equation (147.9 ± 50.2 vs 109.1 ± 32.7 mL/min/1.73 m; p < 0.0001) and higher mean measured creatinine clearance compared with the mean calculated estimated glomerular filtration rate based on the Modification of Diet in Renal Disease equation (147.9 ± 50.2 vs 126.0 ± 41.9 mL/min/1.73 m; p = 0.04). Ninety-four percent of participants with aneurysmal subarachnoid hemorrhage experienced augmented renal clearance on at least 1 day. In patients with intracerebral hemorrhage, there was a higher mean measured creatinine clearance over the study period compared with the mean calculated creatinine clearance (119.5 ± 57.2 vs 77.8 ± 27.6 mL/min/1.73 m; p < 0.0001) and higher mean measured creatinine clearance compared with the mean calculated estimated glomerular filtration rate based on the Modification of Diet in Renal Disease equation (119.5 ± 57.2 vs 93.0.0 ± 32.8 mL/min/1.73 m; p = 0.02). Fifty percent of participants with intracerebral hemorrhage experienced augmented renal clearance on at least 1 day.
A substantial group of patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage experienced enhanced renal clearance, which may be otherwise unknown to clinicians. Enhanced renal clearance may lead to increased renal solute elimination over what is expected, resulting in subtherapeutic renally eliminated drug concentrations. This may result in underexposure to critical medications, leading to treatment failure and other medical complications.
通过测量肌酐清除率评估动脉瘤性蛛网膜下腔出血或脑出血患者的肾功能增强随时间的变化，并将测量的肌酐清除率与 Cockcroft-Gault 方程计算的肌酐清除率和通过肾脏病饮食改良公式计算的估计肾小球滤过率进行比较。
前瞻性观察性研究。
三级保健学术医疗中心的神经科学 ICU。
研究参与者的入院诊断为动脉瘤性蛛网膜下腔出血或脑出血，预计神经科学 ICU 住院时间超过 48 小时，无肾功能障碍证据（入院时血清肌酐 < 1.5mg/dL），且无慢性肾脏病病史。
每天收集 8 小时尿液以测量肌酐清除率，作为测量肾功能的主要方法。还使用 Cockcroft-Gault 方程计算肌酐清除率，并使用肾脏病饮食改良公式计算估计肾小球滤过率。增强的肾清除率定义为测量的肌酐清除率大于 Cockcroft-Gault 和通过肾脏病饮食改良公式计算的估计肾小球滤过率。增强的肾清除率定义为测量的肌酐清除率大于或等于 130mL/min/1.73m。记录相关的人口统计学、临床和结果数据。
50 名动脉瘤性蛛网膜下腔出血患者和 30 名脑出血患者入组，共进行了 590 次个体测量。与基于 Cockcroft-Gault 方程计算的肌酐清除率（147.9±50.2 vs 109.1±32.7mL/min/1.73m；p<0.0001）相比，动脉瘤性蛛网膜下腔出血患者的平均测量肌酐清除率更高，与基于肾脏病饮食改良公式计算的估计肾小球滤过率（147.9±50.2 vs 126.0±41.9mL/min/1.73m；p=0.04）相比，平均测量肌酐清除率更高。94%的动脉瘤性蛛网膜下腔出血患者至少有 1 天出现增强的肾清除率。在脑出血患者中，研究期间的平均测量肌酐清除率高于基于 Cockcroft-Gault 方程计算的肌酐清除率（119.5±57.2 vs 77.8±27.6mL/min/1.73m；p<0.0001），也高于基于肾脏病饮食改良公式计算的估计肾小球滤过率（119.5±57.2 vs 93.0±32.8mL/min/1.73m；p=0.02）。50%的脑出血患者至少有 1 天出现增强的肾清除率。
大量的动脉瘤性蛛网膜下腔出血或脑出血患者出现了肾功能增强，这可能是临床医生所不知道的。增强的肾清除率可能导致比预期更多的肾脏溶质清除，从而导致治疗窗内的肾脏清除药物浓度降低。这可能导致关键药物暴露不足，导致治疗失败和其他医疗并发症。
