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大剂量持续输入解磷定比低剂量快速注射治疗有机磷中毒更有效。在临床试验中，研究人员发现在大剂量疗法之后，呼吸衰竭的症状明显减低，而且人的存活率明显改善。

Kirti S. Pawar医生注意到，在亚洲每年都有成百上千的人们自杀，而他们首选的自杀方式就是喝含有机磷的农药。阿托品和肟疗法是最常用的疗法，但是肟的疗效和最适给药方案还没建立起来。

笔者提到，阿托品是最常用的抑制毒蕈碱受体中乙酰胆碱活性的药物。而用肟治疗的方法却存在很多争议，因为他可以使被抑制了的乙酰胆碱酯酶重新活化。在亚洲肟的标准疗法采用每4－6个小时应用1g肟的剂量。

Dr. Pawar和他的同事进行了一项有200个病人的临床试验，病人年龄为12岁或以上，他们都在该医院治疗不超过（平均2个小时）24小时以后，而且他们的病情稳定。

对所有的病人的初始疗法是在30分钟内，应用负荷剂量（为2g）的碘解磷定同时加入一定剂量的阿托品（剂量由1.8mg－3.0mg不等）。随后就随机的分成两个组：在实验组中，病人们在48小时内不间断的恒量注入解磷定，平均每小时1g。在对照组中，采用标准疗法注入解磷定，1g/hr，在48小时内每4小时注射一次。在48小时的治疗后，所有的病人都以1g/4hr的方式给药，直至病人们可以恢复呼吸功能。

从所有测量的结果来看，实验组的病人疗效更好。Dr. Pawar研究小组报道，实验组与对照组之间的不同在于：平均阿托品用量实验组为16mg，对照组为30mg；平均换气持续时间实验组为5天，对照组为10天；需要借助喉管插管疗法的，实验组为2.7％，对照组为61.3％。

实验组的疗法还降低了死亡率（实验组死亡率为1％，对照组为8％），同时也减少了肺炎的发生率（实验组肺炎发生率为8％，对照组为35％）。

医生们吃惊地发现，此疗法基本没什么副作用比如恶心、呕吐的发生。调查继续了一年之后，也没有后遗症或是神经疾病的发生。

Dr. Pawar和他的同事指出，“不幸的是，解磷定的价格昂贵。我们采用的高剂量疗法在最初的48小时里需要花费400美金，这远远超出了亚洲地区患病农民的经济承担能力。”与此同时，Dr. Peter Eyer and Dr. Nicholas Buckley呼吁人们研制一种降低解磷定生产成本的方法，以期能在发展中国家应用此疗法治疗农药中毒。

他们补充到，“我们相信这个药物能拯救很多生命，尤其是在科技不发达的地区，他们的死亡仅仅是因为没有呼吸器等一些病人需要的高科技医疗器械。”

High-Dose Pralidoxime Effective Treatment for Pesticide Poisoning

NEW YORK (Reuters Health) Dec 14 - Constant, high-dose infusions of pralidoxime appear to be more effective than lower-dose bolus infusions for the treatment of organophosphorus pesticide poisoning, investigators in India report. In their clinical trial, they observed that the severity of respiratory failure is reduced and survival is improved after the high-dose treatment.

Intentional ingestion of organophosphorus pesticides is the primary means of suicide in Asia, killing hundreds of thousands of people every year, Dr. Kirti S. Pawar and associates note in the December 16th issue of The Lancet. Atropine and oxime treatment is the most common regimen, but the effectiveness of oxime treatment and the optimum dose schedule have not been established.

Atropine is commonly administered to inhibit the effects of acetylcholine at muscarinic receptors, the authors note. More controversial is treatment with oximes, which reactivate the inhibited acetylcholinesterase. In Asia, a dose of 1 gram oxime every 4 to 6 hours has become standard treatment.

Dr. Pawar, from Giriraj Hospital and Intensive Care Unit in Pawar, Maharashtra, and colleagues conducted a clinical trial with 200 patients, 12 years or older, who presented at the hospital no later than 24 hours after ingestion (median 2 hours) and who were judged to be moderately ill.

The initial treatment for all patients was a 2-gram loading dose of pralidoxime iodide over 30 minutes along with atropine 1.8 to 3.0 mg. The patients were randomized to treatment with a constant infusion of 1 gram over an hour every hour for 48 hours (study group) or a standard regimen of 1 gram pralidoxime over 1 hour every 4 hours for 48 hours (control group).

After 48 hours, all patients were given 1 gram every 4 hours until they could be weaned from ventilators.

The study group had a better response than the control group for all outcomes measured, Dr. Pawar's team reports: The difference between the study group and the control group, respectively, were: median atropine dose on day 1, 6 mg v. 30 mg; median ventilation duration, 5 days v. 10 days; and 2.7% v. 61.3% required intubation.

The study group also had a lower mortality (1% v. 8%) and fewer cases of pneumonia (8% v 35%).

The physicians were surprised to see no substantial adverse effects, such as nausea or vomiting. During a year-long follow-up, no delayed adverse effects or neurological complications were observed.

"Unfortunately, pralidoxime is expensive," Dr. Pawar and associates point out. "Our high-dose regimen costs around $400 for the first 48 hours, which is far beyond the capacity of most patients in rural Asia."

In an accompanying editorial, Dr. Peter Eyer and Dr. Nicholas Buckley, members of the South Asian Clinical Toxicology Research Collaboration, call for development of a less costly pralidoxime preparation for treatment of pesticide poisoning in developing countries.

"We believe the drug will save lives," they add, "particularly in places where high-tech equipment is not available and many die simply because a respirator cannot be provided for every patient who needs one.

Dr. Eyer is at the University of Munich and Dr. Buckley, at Canberra Hospital in Australia.

Lancet 2006;368:2110-2111,2136-2141.

http://www.medscape.com/viewarticle/549434

编辑：蓝色幻想