美沙酮治疗慢性疼痛往往引起心脏毒性
2011-05-30 23:15:26   来源：   作者：  评论：0 点击：

May 24, 2011 (Austin, Texas) — Patients taking high doses of methadone have more cardiovascular risk, warn researchers.
研究者警告，服用大剂量美沙酮的患者可能存在更高的心血管疾病患病风险。

"There is a dose-dependent effect on QTc interval in patients taking more than 120 mg per day," presenter Ricardo Cruciani, MD, from Beth Israel Medical Center in New York City, said here at the American Pain Society 30th Annual Scientific Meeting.
纽约市以色列贝丝医学中心的Ricardo Cruciani 博士在美国疼痛学会第30届学术年会上发言说：“日剂量超过120毫克存在剂量依赖的QT 间期效应。”

Investigators grouped chronic pain patients according to methadone dose and found the highest-dose group showed significantly more QTc prolongation. Lower doses ranged from 10 to 120 mg.
研究者将疼痛患者按美沙酮剂量进行分组，发现最高剂量组出现了显著的QT 间期延长。较小剂量的大小范围是10 到120 mg

Dr. Cruciani's team considered a QT corrected for heart rate prolongation of more than 500 milliseconds as a definite risk for the potentially fatal arrhythmia torsades de pointes. Men with prolongations of more than 430 and 450 and women with increases of 450 and 470 were considered at risk.
Cruciani博士研究小组认为，QT间期延长超过500毫秒是致死性心律失常（扭转性室速）的潜在危险因子。延长430到450毫秒的男性与延长450到470毫秒的女性均被认为是高危人群。

According to the Centers for Disease Control and Prevention (CDC), the number of fatal poisoningscaused by opioid overdoses has tripled in recent years. Leading the pack among analgesic-related deaths is methadone.
根据疾控及预防中心，由鸦片类药物过量引起的致死毒性病例近年增长达到3 倍。美沙酮在痛觉迟缓相关的死因中高居首位。

Rising Death Rate
"Our interpretation is the doses for methadone used to be low," Dr. Cruciani told Medscape Medical News. "For many years it has been used as substitution therapy in treatment programs for patients with opioid addiction. However, in the last decade, methadone to treat chronic pain patients became more common."
Cruciani博士接受访问时说：“我们以前对美沙酮的用量都坚持在小剂量。多年来美沙酮都用作鸦片类成瘾患者的替代药物。然而，在过去十年，美沙酮治疗慢性疼痛变得更为常见。”

Dr. Cruciani suggests the increasing popularity can be attributed to the efficacy, long duration of action, and low cost. Many questions remain about the cause of methadone deaths, but some researchers suggest cardiac toxicity is at play.
Cruciani博士介绍说，美沙酮应用日益增多其中一个重要原因是它的效能，作用时间长及成本低廉。美沙酮引起死亡的原因仍然不清楚，但一些学者认为主要是心脏毒副作用是主要原因。

In the CDC report led by Diane Makuc, DrPH, the team from the National Center for Health Statistics points out the drug is a long-acting opioid and requires a complex dosing schedule. "Methadone relieves pain for 4 to 8 hours but remains in the body for up to 59 hours. A lack of knowledge about the unique properties of methadone was identified as contributing to some deaths."
一份由公共卫生学博士Diane Makuc带领的国家健康统计中心团队在CDC发布的报道指出，美沙酮是一种长效鸦片类制剂，需要根据实际情况作出剂量调整。“美沙酮可以有效作用4到8小时，但可以在体内存在长达59小时。目前仍然缺乏对美沙酮独特性质的了解，这是引起部分死亡的原因之一。”

Another national reviewof unintentional overdose deaths involving opioids came to a similar disturbing conclusion — a disproportionate number of poisonings are related to methadone.
在另一份全国性关于无意致使的鸦片类药物过量致死的回顾分析中，得到了类似的令人担忧的结论：死亡相关的药物毒性作用中，美沙酮独占鳌头。

Presenting at last year's American Academy of Pain Medicine Annual Meeting, investigators reported 30% of deaths involved methadone even though the drug represents only 5% of the nation's opioid prescriptions.
研究者在去年美国疼痛医学学会年度会议上报道了30%与美沙酮相关的死亡个案，即使美沙酮只占了全国鸦片类药物处方的5%。

The researchers, led by Lynn Webster, MD, founder of the Salt Lake City, Utah–based Life Source Foundation, which funded the study, said the problems appeared to center on methadone prescribed for pain not addiction.
由赞助本次研究的犹他州盐湖城生命资源基地成立者Lynn Webster领导的研究组解释道，现有的问题似乎围绕着疼痛引起的美沙酮处方，而非针对成瘾的处方。

In this new study, Dr. Cruciani's team focused on chronic pain patients and especially those older than 50 years, considered at higher cardiovascular risk. Investigators looked at 39 patients taking methadone and wanted to compare the effectiveness of a single electrocardiogram vs a 24-hour Holter monitor in detecting abnormal QT.
在这个新的研究里，Cruciani博士的研究组集中研究慢性疼痛患者，特别是那些年龄大于50岁的，并认为这些人具有较高的心血管疾病患病风险。研究者观察39名服用美沙酮的病人，想要比较单次心电图与24小时心动监测关于检测异常QT间期的效能。

Torsades de Pointes
They found a single electrocardiogram detected fewer patients with QTc interval prolongations compared with a 24-hour Holter monitor (15 vs 20). However, the 2 approaches detected the same number of patients at risk for torsades de pointes.
他们发现单次心电图检查比24小时心动监测发现QT间期延长更少（15 vs 20），然而，两种方法在检测扭转性室速的效能是一样的。

Of note, Holter monitoring detected twice as many patients with QTc prolongations at noon compared with electrocardiogram. "This suggests that a single test might not be sufficient in identifying patients at risk," Dr. Cruciani said.
心动监测发现的QT间期延长的病人数目比普通心电图多1 倍。Cruciani 说道：“这个现象说明了单次检查不足以发现具有患病风险的病人。”

Despite the growing concerns over cardiac toxicity, many investigators suggest methadone deaths are a multipronged problem.
尽管对心脏毒性的担忧与日俱增，仍然有很多学者坚持美沙酮相关的死亡存在多种解释。

Dr. Webster's team studied malpractice cases in the United States, searched the literature, and reviewed other local and federal sources of information and found many reasons for the rising death toll.
Webster博士的团队回顾了美国医疗过失的个案、搜索文献并回顾了其他州及美国联邦范围内相关资料，发现死亡率上升由多种原因造成。

"There's not one thing that caused this," Dr. Webster said when first presenting the results of his study. "There are multiple things that all add up."
Webster 博士在首次展示研究成果时说：“并非只有一个原因造成这种现象。其中存在很多方面的因素对此现象作了贡献。”

A chief reason, his team suggests, is that conversion tables — used by physicians to transition patients from one opioid to another — recommend too much methadone for most patients. For example, Dr. Webster pointed out, through 2006, the US Food and Drug Administration recommended a starting dose of 80 mg per day. That recommendation has since been changed to 30 mg a day.
他的团队表示，主要的原因是临床医师用于给服用鸦片类药物患者进行药物替换的指导表格的推荐剂量往往过大。例如，在2006年，美国FDA推荐的起始剂量为80毫克每日。这个剂量从那以后就变成30毫克每日了。

"For most individuals, starting them at 80 mg per day, they would die," Dr. Webster said.
“对大多数的患者来说，以80毫克每日为起始剂量会导致病人最后的死亡。”

"We used to regularly see doses of 40 or 60 mg," Dr. Cruciani told Medscape Medical News. "This was when methadone was used primarily for addiction, but now that we use it for chronic pain we choose much higher doses."
“我们过往推荐的剂量一般为每日40到60毫克，这是美沙酮被用作戒瘾用途的剂量。但现在我们选择更大剂量来治疗慢性疼痛。”