低钠血症增加择期手术后死亡风险

《内科学文献》(Archives of Internal Medicine) 9月10日在线发表的一项观察性研究表明，在近100万例接受大手术的成年患者中，低钠血症患者在术后30天内死亡的风险比无低钠血者高44% (doi:10.1001/archinternmed.2012.3992)。

美国波士顿布里格姆妇女医院的Alexander A. Leung博士及其同事以2005年1月~2010年12月在200多家医院接受大手术的964,263例成年患者为研究对象，对其30天围手术期结局进行了评估。入选该研究的所有患者都有术前血清钠数据。

低钠血症定义为血清钠水平低于135 mEq/L，见于7.8%的受试者，其中89%属于“轻度”低钠血症。针对潜在混杂因素进行校正后，术前存在任何程度低钠血症的患者术后30天内死亡的风险为5.2%，而没有低钠血症的患者死亡风险只有1.3%(校正比值比[aOR]，1.44；95%置信区间[CI]，1.38~1.50)。

Leung博士指出：“我们已知低钠血症是心衰、肝病、肾病和肺炎患者的不良预后因子之一，而这项研究首次证明了低钠血症与术后死亡风险增加相关。术前哪怕只有轻度低钠血症也可能导致严重的后果，因此不容忽视。”

而且在接受择期手术的患者中，与低钠血症相关的死亡风险更高(aOR，1.59；95%CI，1.50~1.69)；在术前健康状况最好(依照美国麻醉师协会标准，术前健康状况为1级或2级)的受试者亚组中死亡风险增加更为显著(aOR，1.93；95%CI，1.57~2.36)。

除了死亡风险增加以外，研究者还发现存在低钠血症还与患病风险显著增加相关，包括重大冠脉事件(1.8% vs. 0.7%；aOR，1.21；95%CI，1.14~1.29)，伤口感染(7.4% vs. 4.6%；aOR，1.24；95%CI，1.20~1.28)和肺炎(3.7% vs. 1.5%；aOR，1.17；95%CI，1.12~1.22)。

此外，低钠血症患者的中位住院时间也延长了1天左右。研究者指出，还需开展进一步的研究以明确是低钠血症本身导致了不良事件还是仅仅提示了患者存在其他可能导致死亡和患病风险增加的潜在严重疾病。

研究者并未就术前发现低钠血症应如何纠正给出明确的临床建议。他们认为短时间内迅速调整血钠水平“可能会很危险”，不过，“如果确认在密切监测的前提下纠正低钠血症是安全且有益的”就另当别论了。

研究者认为：“目前合理的做法是密切监测所有危险患者的围手术期并发症；如果发现了可逆转的潜在原因，则建议在非急诊手术前选择性地治疗低钠血症。”

研究者还指出了这项研究的一些局限性，包括观察性设计、可能存在未测定的混杂因素、缺少用药数据以致于无法确定不同的药物暴露是否会令患者的风险发生改变。

这项研究的部分经费来自Alberta Innovates–Health Solutions和加拿大卫生研究院。Leung博士及其同事声明无相关经济利益冲突。

随刊述评：提出治疗问题

术前低钠血症与围手术期不良结局之间的关系涉及到许多关键的治疗问题。应如何治疗术前低钠血症？术前专科会诊和联合管理是否能降低低钠血症的风险或及时、安全地改善血钠水平？血管加压素受体拮抗剂治疗对于术前低钠血症是否有效？重症患者需要立即接受诊断性评估并考虑推迟手术时间以便纠正低钠血症，尤其是择期手术患者。不过，轻度低钠血症要常见得多，对于这类合并症至少需要各专科间的合作以确保术前患者处于最佳状态。此外，还需要考虑到有的合并症可能没有诊断出来。

这项研究的结果还不能确定是否应该推迟择期手术以治疗轻度低钠血症，但低钠血症的诊断对于术前的知情同意程序很有帮助。挑战在于如何确定后续步骤。虽然理论上讲是应该直接处理低钠血症，但不清楚这样的治疗对于择期手术时间的确定应该产生多大的影响……根据患者的合并症病情以及计划施行的手术操作，对低钠血症进行个性化的处理可能是确定干预措施实施顺序的唯一办法。

随刊述评作者JOSEPH A. VASSALOTTI博士和ERIN DUPREE博士来自美国纽约西奈山医疗中心。他们都声明无相关利益冲突。

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By: JENNIE SMITH, Clinical Endocrinology News Digital Network

An observational study of nearly 1 million adults undergoing major surgery has found that those with hyponatremia saw a 44% increased risk of death within 30 days of surgery, compared with subjects without the disorder.

Hyponatremia is already a known negative prognostic factor in heart failure, liver disease, kidney disease, and pneumonia. The new study, published online Sept. 10 in Archives of Internal Medicine (doi:10.1001/archinternmed.2012.3992), marks the first time that hyponatremia has been linked to higher risk of postsurgical mortality. Patients with any degree of hyponatremia before surgery saw a 5.2% risk of death, compared with 1.3% for patients without the disorder, even after the researchers adjusted for potential confounders (adjusted odds ratio 1.44; 95% confidence interval, 1.38-1.50).

Adding to this stark finding was the fact that among patients undergoing elective surgery, the mortality risk associated with hyponatremia was even higher (aOR 1.59; 95% CI 1.50-1.69) and more pronounced still among a subgroup of subjects considered the healthiest preoperative candidates, those with a class 1 or 2 status according to American Society of Anesthesiologists criteria (aOR 1.93; 1.57-2.36).

For their research, investigators Dr. Alexander A. Leung of Brigham and Women’s Hospital, Boston, and his colleagues, identified 964,263 adults undergoing major surgery from more than 200 hospitals between from January 2005 through December 2010 and evaluated their 30-day perioperative outcomes. Presurgery serum sodium levels were available for all patients included in the study.

Hyponatremia, defined as a serum sodium level of less than 135 mEq/L, occurred in 7.8% of all study patients, with 89% of these cases classified as "mild."

Dr. Leung and his colleagues wrote that their findings show that even mild hyponatremia preceding surgery is "not inconsequential and should not be ignored." In addition to the increased mortality risk, the investigators also found the presence of hyponatremia to be associated with significantly increased risk of morbidity, including major coronary events (1.8% vs. 0.7%; aOR 1.21; 95% CI 1.14-1.29), wound infections (7.4% vs. 4.6%; 1.24; 1.20-1.28), and pneumonia (3.7% vs. 1.5%; 1.17; 1.12-1.22).

Also, median length of hospital stay was prolonged by approximately 1 day among subjects with hyponatremia.

Dr. Leung and his colleagues wrote in their analysis that further research was needed to clarify whether hyponatremia caused adverse events or whether it merely indicated the presence of other serious underlying conditions contributing to morbidity and mortality.

The authors stopped short of making explicit clinical recommendations about correcting hyponatremia when it is detected prior to surgery.

Inducing rapid changes to sodium levels in a short period of time "can be potentially disastrous," the investigators wrote. However, "if monitored correction of hyponatremia is found to be safe and beneficial, it would strengthen causal inference and would be transformative to routine care since serum sodium is not presently recognized as an independent and reversible risk factor for perioperative complications."

Until further studies establish that reversing hyponatremia before surgery does in fact reduce risk, "one reasonable approach is to monitor for perioperative complications in all patients at risk and to selectively treat hyponatremia before nonemergency surgical procedures when a reversible cause is found," Dr. Leung and his colleagues wrote.

The investigators noted among the weaknesses of their study its observational design, the potential existence of unmeasured confounders, and a lack of medication data that did not allow them to determine how risk may vary according to different drug exposures.

Dr. Leung and his colleagues’ study was supported in part by Alberta Innovates–Health Solutions and the Canadian Institutes for Health Research. They reported having no relevant conflicts of interest.

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Therapeutic Questions Raised

The association of preoperative hyponatremia with adverse perioperative outcomes raises a variety of key therapeutic questions. How should preoperative hyponatremia be treated? Can preoperative medical consultation and comanagement attenuate the risk of hyponatremia or improve the serum sodium concentration in a timely and safe manner? Is there a role for vasopressin receptor antagonist therapy in preoperative hyponatremia? Severe cases require an immediate diagnostic evaluation and consideration for postponement of surgery to allow for correction, particularly if the case is elective. Mild hyponatremia, though, is the much more common situation, and, at a minimum, comorbidities require collaboration among specialties to ensure that the patient’s condition is optimized before surgery. In addition, the possibility of undiagnosed comorbidities needs to be considered.

Whether elective surgery should be postponed for the treatment of mild hyponatremia cannot be ascertained from this study, but the diagnosis should contribute to the informed consent process. The challenge lies in determining the next steps. Although the algorithm is relatively straightforward for treating hyponatremia, it is unclear how much this treatment should factor into a decision to proceed with elective surgical procedures. ... An individualized approach considering hyponatremia in the context of the patient’s comorbidities and the planned surgical procedure can be the only guide to the sequence of interventions.

JOSEPH A. VASSALOTTI, M.D., and ERIN DUPREE, M.D., are with Mount Sinai Medical Center, New York. They reported having no relevant disclosures.

学科代码：内科学 外科学 全科医学　　　关键词：低钠血症增加择期手术后死亡风险
来源： EGMN