Sorani Marco D, Manley Geoffrey T
Program in Biological and Medical Informatics, University of California, San Francisco, CA 94110, USA.
J Neurosurg. 2008 Jan;108(1):80-7. doi: 10.3171/JNS/2008/108/01/0080.
Brain edema can increase intracranial pressure (ICP), potentially leading to ischemia, herniation, and death. Edema and elevated ICP are often treated with osmotic agents to remove water from brain tissue. Mannitol is the osmotic diuretic most commonly used in the intensive care unit; however, despite its clinical importance, treatment protocols vary from center to center, and the dose-response relationship is not understood. The goal of this metaanalysis was to aggregate and analyze data from studies in which authors have described the dose-response relationship between mannitol and ICP.
The authors identified 18 studies that quantitatively characterized the dose-response relationship of mannitol and ICP. We also examined study designs and mannitol administration protocols.
Meta-regression found a weak linear relationship between change in ICP (delta ICP) and dose (delta ICP = 6.6 x dose - 1.1; p = 0.27, R(2) = 0.05). The lack of statistical significance could reflect the variation in protocols among studies and the variation in patients both within and among studies. However, the authors found a highly significant difference (p < 0.001) in decrease in ICP when the initial ICP was higher or lower than 30 mm Hg. Nonlinear regression suggested that ICP decrease is greatest shortly after mannitol is given (R(2) = 0.63). Finally, the authors found that recent studies tend to include fewer patients and set a lower ICP threshold for mannitol administration but report more parameters of interest; the duration of mannitol's effect was the most frequently unreported parameter.
Despite its clinical importance, the determination of the mannitol dose-response curve continues to be challenging for many reasons. This metaanalysis highlights the need for a consensus of methods and results required to determine this important relationship.
脑水肿可升高颅内压（ICP），有可能导致缺血、脑疝和死亡。水肿及升高的颅内压常采用渗透性药物治疗，以从脑组织中清除水分。甘露醇是重症监护病房最常用的渗透性利尿剂；然而，尽管其具有临床重要性，但各中心的治疗方案各不相同，且剂量-反应关系尚不明确。本荟萃分析的目的是汇总和分析作者描述甘露醇与颅内压之间剂量-反应关系的研究数据。
作者识别出18项定量描述甘露醇与颅内压剂量-反应关系的研究。我们还检查了研究设计和甘露醇给药方案。
Meta回归发现颅内压变化（ΔICP）与剂量之间存在微弱的线性关系（ΔICP = 6.6×剂量 - 1.1；p = 0.27，R² = 0.05）。缺乏统计学意义可能反映了研究间方案的差异以及研究内和研究间患者的差异。然而，作者发现当初始颅内压高于或低于30 mmHg时，颅内压降低存在高度显著差异（p < 0.001）。非线性回归表明，甘露醇给药后不久颅内压降低最为显著（R² = 0.63）。最后，作者发现近期研究纳入的患者往往较少，设定的甘露醇给药颅内压阈值较低，但报告的感兴趣参数更多；甘露醇作用持续时间是最常未报告的参数。
尽管甘露醇具有临床重要性，但由于多种原因，确定甘露醇剂量-反应曲线仍然具有挑战性。本荟萃分析强调了在确定这一重要关系所需的方法和结果方面达成共识的必要性。
