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.