Morbitzer Kathryn A, Jordan J Dedrick, Rhoney Denise H
Division of Practice Advancement and Clinical Education, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 115 Beard Hall, Campus Box 7574, Chapel Hill, NC, 27599, USA.
Neurocrit Care. 2015 Apr;22(2):258-64. doi: 10.1007/s12028-014-0079-4.
Therapeutic strategies that cause an alteration in patient temperature, such as controlled normothermia (CN), therapeutic hypothermia (TH), and pentobarbital infusion (PI), are often used to manage complications caused by acute brain injury. The purpose of this study was to evaluate pharmacokinetic (PK) parameters of vancomycin in patients with acute brain injury undergoing temperature modulation.
This was a retrospective cohort study of adult patients with acute brain injury admitted between May 2010 and March 2014 who underwent CN, TH, or PI and received vancomycin. Predicted PK parameters based on population data were compared with calculated PK parameters based on serum concentrations.
Seventeen CN patients and 10 TH/PI patients met inclusion criteria. Traumatic brain injury and aneurysmal subarachnoid hemorrhage accounted for the majority of admitting diagnoses. In the CN group, the median dose was 16.7 (15.5-18.4) mg/kg. The median calculated elimination rate constant [0.155 (0.108-0.17) vs. 0.103 (0.08-0.142) hr(-1); p = 0.04] was significantly higher than the predicted value. The median measured trough concentration [8.9 (7.7-11.1) vs. 17.1 (10.8-22.3) υg/mL; p = 0.004] was significantly lower than predicted. In the TH/PI group, the median dose was 15.4 (14.7-17.2) mg/kg. No significant differences were found between the median calculated and predicted elimination rate constant [0.107 (0.097-0.109) vs. 0.112 (0.102-0.127) hr(-1); p = 0.41] and median measured and predicted trough concentration [14.2 (12.7-17.1) vs. 13.1 (11-17.8) υg/mL; p = 0.71].
Patients who underwent TH/PI did not exhibit PK alterations when compared to predicted PK parameters based on population data, while patients who underwent CN experienced PK alterations favoring an increased elimination of vancomycin.
引起患者体温改变的治疗策略，如控制性正常体温（CN）、治疗性低温（TH）和戊巴比妥输注（PI），常用于处理急性脑损伤引起的并发症。本研究的目的是评估接受体温调节的急性脑损伤患者中万古霉素的药代动力学（PK）参数。
这是一项回顾性队列研究，研究对象为2010年5月至2014年3月间收治的接受CN、TH或PI并接受万古霉素治疗的成年急性脑损伤患者。将基于群体数据预测的PK参数与基于血清浓度计算的PK参数进行比较。
17例CN患者和10例TH/PI患者符合纳入标准。创伤性脑损伤和动脉瘤性蛛网膜下腔出血占大多数入院诊断。在CN组中，中位剂量为16.7（15.5 - 18.4）mg/kg。计算出的中位消除速率常数[0.155（0.108 - 0.17）对0.103（0.08 - 0.142）hr⁻¹；p = 0.04]显著高于预测值。测量的中位谷浓度[8.9（7.7 - 11.1）对17.1（10.8 - 22.3）μg/mL；p = 0.004]显著低于预测值。在TH/PI组中，中位剂量为15.4（14.7 - 17.2）mg/kg。计算出的中位消除速率常数与预测值之间[0.107（0.097 - 0.109）对0.112（0.102 - 0.127）hr⁻¹；p = 0.41]以及测量的中位谷浓度与预测值之间[14.2（12.7 - 17.1）对13.1（11 - 17.8）μg/mL；p = 0.71]均未发现显著差异。
与基于群体数据预测的PK参数相比，接受TH/PI的患者未表现出PK改变，而接受CN的患者出现了有利于增加万古霉素消除的PK改变。
