Tan Ge, Zhou Jiying, Yuan Dongli, Sun Shanquan
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Clin Drug Investig. 2008;28(2):81-7. doi: 10.2165/00044011-200828020-00002.
Although mannitol has been widely used in hospitals to treat patients with high intracranial pressure (ICP) secondary to intracerebral haemorrhage (ICH), no universal agreement has been reached regarding the optimal dosage of this agent for achieving appropriate intracranial decompression. The aim of this study was to investigate the effects of different mannitol dosages on ICP and the effects of other factors, such as sex, age, haemorrhage location and haematoma volume, on the ICP-lowering effect of mannitol. The data obtained were then used to construct a formula for estimating the total dosage of mannitol required to reduce ICP in individual patients with ICH.
A total of 72 patients with ICH and elevated ICP monitored in our intensive care unit were included in this study. Patients with ICH who had hypoxaemia (arterial oxygen saturation <90%), severe functional disturbances of the liver or kidney, acidosis or pathological changes in the visual conducting pathway were not included in this study. Each patient received 20% intravenous mannitol 125 mL every 4, 6 or 8 hours per day to treat elevated ICP, with ICP levels being measured before administration of mannitol and at least three times per day during administration of the drug. When the ICP reached a fixed level, the dosage of mannitol was gradually reduced. The total dosage of mannitol used to reduce the ICP from the highest value to the fixed value was calculated. Data on the patients' sex, age, haemorrhage location and haematoma volume were also obtained. Multivariate regression analysis of the results enabled development of a formula for use of mannitol in patients with ICH and elevated ICP.
Use of mannitol significantly decreased ICP in all patients. The effect of mannitol on ICP reduction was dose-dependent during the period of ICP reduction (p < 0.05) but not after the ICP had reached a fixed level; this limited effectiveness of mannitol when its dosage reaches a certain level was termed 'mannitol saturation dosage'. The reduction in ICP with mannitol was not statistically significantly affected by the patient's sex or age, but was significantly correlated with both haemorrhage location and haematoma volume (p < 0.05). The reduction in ICP with mannitol was greater in patients with supratentorial ICH compared with those with infratentorial ICH (p < 0.0001).
The total mannitol dosage required for individual patients with ICH and elevated ICP can be calculated by considering the location of the haemorrhage, the volume of the haematoma and the pretreated ICP reading. To this end, the following formula was derived in the study: Total dosage of mannitol (mL of 20% mannitol) = (x + 31.17900 x y - 3.39853 x z - 244.47590)/0.00752, where x = the pretreated ICP (mmH(2)O), y = the haemorrhage location (supratentorial ICH: y = 0, infratentorial ICH: y = 1) and z = the volume of haematoma (mL). Use of this formula in the clinical setting should help reduce the possibility of adverse effects resulting from administration of excessive dosages of mannitol.
尽管甘露醇已在医院中广泛用于治疗继发于脑出血(ICH)的颅内压(ICP)升高患者,但关于该药物达到适当颅内减压的最佳剂量尚未达成普遍共识。本研究的目的是探讨不同剂量甘露醇对ICP的影响,以及性别、年龄、出血部位和血肿体积等其他因素对甘露醇降低ICP效果的影响。然后将获得的数据用于构建一个公式,以估算个体ICH患者降低ICP所需的甘露醇总剂量。
本研究纳入了在我们重症监护病房监测的72例ICH且ICP升高的患者。排除存在低氧血症(动脉血氧饱和度<90%)、严重肝肾功能障碍、酸中毒或视传导通路病变的ICH患者。每位患者每天每4、6或8小时静脉注射20%甘露醇125 mL以治疗ICP升高,在注射甘露醇前及用药期间每天至少测量3次ICP水平。当ICP达到固定水平时,逐渐减少甘露醇剂量。计算将ICP从最高值降至固定值所用的甘露醇总剂量。还获取了患者的性别、年龄、出血部位和血肿体积数据。对结果进行多变量回归分析,得出了用于ICH且ICP升高患者的甘露醇使用公式。
甘露醇的使用使所有患者的ICP显著降低。在ICP降低期间,甘露醇降低ICP的效果呈剂量依赖性(p<0.05),但在ICP达到固定水平后则不然;当甘露醇剂量达到一定水平时其有限的有效性被称为“甘露醇饱和剂量”。甘露醇降低ICP的效果在统计学上不受患者性别或年龄的显著影响,但与出血部位和血肿体积均显著相关(p<0.05)。与幕下ICH患者相比,幕上ICH患者使用甘露醇降低ICP的幅度更大(p<0.0001)。
对于个体ICH且ICP升高的患者,可通过考虑出血部位、血肿体积和预处理的ICP读数来计算所需的甘露醇总剂量。为此,本研究得出以下公式:甘露醇总剂量(20%甘露醇毫升数)=(x + 31.17900×y - 3.39853×z - 244.47590)/0.00752,其中x =预处理的ICP(mmH₂O),y =出血部位(幕上ICH:y = 0,幕下ICH:y = 1),z =血肿体积(mL)。在临床环境中使用该公式应有助于降低因过量使用甘露醇导致不良反应的可能性。