Rudis Maria I, Touchette Daniel R, Swadron Stuart P, Chiu Amy P, Orlinsky Michael
Department of Pharmacy, School of Pharmacy Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Ann Emerg Med. 2004 Mar;43(3):386-97. doi: 10.1016/j.annemergmed.2003.10.011.
Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations.
A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED.
The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse events. With time to safe ED discharge as the outcome measure, the incremental cost-effectiveness ratios were 3.90 dollars and 387.27 dollars per hour of ED time saved for oral phenytoin versus intravenous phenytoin and for intravenous fosphenytoin versus intravenous phenytoin, respectively.
Oral phenytoin is the most cost-effective loading method in most settings. Intravenous phenytoin is preferred if one is willing to pay an additional 20.65 dollars to 44.25 dollars per patient and willing to have more adverse events for a quicker average time to safe ED discharge. It is unlikely that intravenous fosphenytoin is justifiable in any setting.
口服苯妥英钠、静脉注射苯妥英钠和静脉注射磷苯妥英钠在急诊科（ED）均常用于苯妥英钠的负荷给药。对癫痫发作且苯妥英钠浓度低于治疗水平的患者比较了每种给药方式的成本效益。
构建一个简单的决策树以确定三种负荷给药技术各自的治疗成本。通过比较不良事件发生率以及计算安全出院所需时间来确定有效性。安全出院所需时间定义为达到苯妥英钠治疗浓度（≥10mg/L）且无任何妨碍出院的不良事件发生的时间。通过将净成本与不良事件数量相结合（以避免的不良事件成本表示）来确定口服苯妥英钠替代方案的比较成本效益。还通过比较达到安全出院所需时间的每种负荷给药技术的净成本（以节省的每小时急诊时间成本表示）来确定成本效益。结果和成本主要来自一项前瞻性随机对照试验，并通过时间动作研究和替代成本来源进行补充。成本包括药品、耗材和人员成本。还在纳入劳动力成本以及使用急诊较低紧急程度区域所节省费用的情况下进行了分析。
口服苯妥英钠、静脉注射苯妥英钠和静脉注射磷苯妥英钠每组患者的平均不良事件数分别为1.06、1.93和2.13。三组安全出院的平均时间分别为6.4小时、1.7小时和1.3小时。每位患者的成本分别为2.83美元、21.16美元和175.19美元，在劳动力和分诊（急诊较低紧急程度区域）情况下差异不大。当以不良事件作为有效性衡量指标时，口服苯妥英钠优于静脉注射苯妥英钠和静脉注射磷苯妥英钠，成本和不良事件数量均较低。以安全出院所需时间作为结果衡量指标时，口服苯妥英钠与静脉注射苯妥英钠相比以及静脉注射磷苯妥英钠与静脉注射苯妥英钠相比，每节省一小时急诊时间的增量成本效益比分别为3.90美元和387.27美元。
在大多数情况下，口服苯妥英钠是最具成本效益的负荷给药方法。如果愿意为每位患者额外支付20.65美元至44.25美元，并且愿意为更快的平均安全出院时间承受更多不良事件，则首选静脉注射苯妥英钠。在任何情况下，静脉注射磷苯妥英钠都不太合理。
