专家组支持静注苯肾上腺素治疗围手术期低血压

马里兰州银泉市——在9月13日的一次会议上，FDA的管理顾问专家组一致同意，多年来在麻醉过程中、重症监护病房和其他情况下广泛用于低血压患者升压治疗的静脉注射苯肾上腺素，应被批准在椎管内麻醉中作为低血压患者的升压治疗。但在本次会议上，心血管和肾脏药物顾问委员会以8:2的票数反对批准将静脉注射苯肾上腺素作为在急性低血压状态下(如休克)的升压治疗，原因是相关研究数据不足。

苯肾上腺素是一种选择性1肾上腺能受体激动剂，已经被使用了几十年，由于当时尚未建立现行的药品批准程序，所以未经过FDA核准，FDA认为这是一种有医学必要性的未核准药品。

遵照FDA未批准药品倡议的规定，West-Ward制药公司提交了一份将静脉注射苯肾上腺素用于“在急性低血压状态下(如休克和围手术期低血压)作为升压治疗”的申请。这份申请包含50项已发表的研究，多数是针对在剖宫产手术中接受椎管麻醉的低危妇女的研究。会议上，公司高层领导人和代表公司发言的临床医生总结了20世纪80年代至2010年间发表的这些研究的结果。

仅有8项研究是在脓毒血症或感染性休克患者中进行的，因此FDA认为关于在这一人群中应用静脉苯肾上腺素的获益和风险的认识十分有限，并且没有关于静脉注射苯肾上腺素用于治疗其他类型休克的研究。对于椎管内麻醉以外的适应证，在获得批准之前还需要更多数据，包括关于对终末器官损害的疗效和治疗影响的数据。作为两位投票支持批准全部适应证的专家之一的Joseph Tobin医生，是北卡罗来纳州温斯顿-塞勒姆市Wake Forest Baptist 医院的麻醉科和儿科教授，他认为30多年的应用经验表明在这两种适应证上的应用都是合理的。

FDA通常会接受其顾问专家组的建议。专家组成员披露无相关利益冲突。

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By: ELIZABETH MECHCATIE, Cardiology News Digital Network

SILVER SPRING, MD. – Intravenous phenylephrine, used widely for decades to increase blood pressure in patients who become hypotensive during anesthesia, in intensive care, and in other situations, should be approved for use to increase blood pressure in patients who become hypotensive during neuraxial anesthesia, a Food and Drug Administration advisory panel unanimously agreed at a meeting on Sept. 13.

However, at the meeting the Cardiovascular and Renal Drugs Advisory Committee voted 8 to 2 against recommending approval of IV phenylephrine as a treatment to increase blood pressure in acute hypotensive states, such as shock, because more studies are needed.

IV phenylephrine, a selective alpha1-adrenergic receptor agonist, has been used for decades without being approved by the FDA, since it was available before the current drug approval process was established, and is one of the unapproved products that the FDA considers medically necessary.

As a result of the FDA’s Unapproved Drugs Initiative, West-Ward Pharmaceuticals submitted an application for approval of intravenous phenylephrine "to increase blood pressure in acute hypotensive states, such as shock and perioperative hypotension." The application included 50 published studies, mostly of low-risk women who had neuraxial anesthesia during cesarean delivery.

At the meeting, company officials and clinicians who spoke on behalf of the company summarized the results of these studies, published from the 1980s through 2010.

Only eight studies were in patients with sepsis or septic shock, so the benefits and risks of IV phenylephrine for this use were limited, and there were no studies on the use of IV phenylephrine as a treatment for other types of shock, according to the FDA.

For indications other than neuraxial anesthesia, more data are needed before approval, including more data on efficacy and the impact of treatment on end-organ damage, said panel chair Dr. A. Michael Lincoff, professor of medicine at the Cleveland Clinic.

One of the two panelists voting in favor of approval for the full indication (including acute hypotensive episodes due to shock), Dr. Joseph Tobin, professor of anesthesiology and pediatrics at Wake Forest Baptist Health, Winston-Salem, N.C., said that he felt comfortable after 30 years of use with this drug for the full indication, as proposed by the company.

The FDA usually follows the recommendations of its advisory panels. Panel members had no conflicts to disclose.

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