Marathons and Hyponatremia

A review of two studies

I love it when some of the arcane nephrology knowledge makes headlines. When I heard NPR covering hyponatremia I almost cried. At the time I was training for a half marathon and so I had been thinking about this topic.

NPR was reporting on Almond, Et al’s study in the NEJM. The investigators looked at 488 blood samples from 766 runners recruited from the 2002 Boston Marathon. They found post-race:

• 13% had a sodium less than 135
• 22% in women
• 8% in men

Three people had critical sodiums (118, 119, 114)

When they looked at predictors of hyponatremia, univariate predictors included:

• Female gender (p<0.001)
• BMI less than 20 (p=0.03)
• Fewer prior marathons (p=0.008)
• Slower training pace (p<0.001) and longer race duration (p<0.001)
• Increased hydration frequency (p<0.001) and volume (p=0.01)
• Urination during the race (with more frequent voiding having a higher risk of hyponatremia) (p=0.047)

But the big elephant in the room was weight gain during the race (p<0.001).

Of note use of sport drinks compared to pure water made no difference. In the multivariate analysis, hyponatremia was associated with:

• weight gain
• longer racing time
• body-mass index of less than 20

Here are the authors on the implications of the results:

If our sample was representative of the overall 2002 Bos- ton Marathon field of runners, we would estimate that approximately 1900 of the nearly 15,000 finish- ers had some degree of hyponatremia, and that ap- proximately 90 finishers had critical hyponatremia.

The Almond study was high profile and did a good job of demonstrating the risk factors for marathon induced hyponatremia. However, it’s prmary finding is a bit self evident: increased weight gain (presumably water gain) is associated with hyponatremia. What is not answered is, why people accumulate three liters of water. Why don’t these runners just urinate the excess water? Normally, a falling sodium, shuts down ADH like a bordello on Easter. The retention of water is indirect evidence of ADH. Could it be that marathon running and ultra-endurance events could be added to the list of causes of the Syndrome of Anti Diuretic Hormone (SIADH).

It would have been nice to see a U/A or urine osmolality in Almond’s data to confirm this.

Siegel et al. (PDF) has done the most detailed study on exercise induced hyponatremia. They did detailed biochemical assessments on 39 runners in the 2001 Boston Marathon. They drew pre-race (day before) and post-race (within 2 hous of finishing) samples for sodium, ADH and a handful of other biochemical markers.

They also looked at 308 runners who collapsed during the 2004 Boston Marathon and measured IL-6 and ADH.

Lastly, they reported on the blood tests from tworunners who died of cerebral edema from exercise induced hyponatremia. One from the 2002 Marine marathon and the other from the 2002 Boston Marathon.

Of the 308 collapsed runners only 16 had hyponatremia. All of the hyponatremic runners reported a lack of urination during the race. 7 of the 16 had inappropriately high ADH levels in the blood. The authors concluded that lack of urination (though only driven by ADH in half the patients) rather than fluid loading was the predominant cause of hyponatremia.

The article then describes the laboratory and clinical scenario surrounding the two deaths in 2002. The data is summarized in the following table:

Importantly, both patients were initially treated with 150 mL/hr of normal saline without improvement. Two years later, two patients presented with similar symptoms and responded well to 3% saline:

The primary conclusions from this study, which admittedly is a bit schizophrenic with numerous anecdotal reports from various populations, is that exercise induced hyponatremia is not due to sodium loss but rather from fluid retention. Some of this fluid retention is driven by ADH and hence introduces exercise induced hyponatremia as a novel cause of SIADH. The diagnosis of SIADH is backed up by elevated urine sodium, elevated urine osmolality and normal cortisol and TSH levels.

The elevated urinary sodium levels (consistent with SIADH) are a critical finding in this study. If we were dealing with hypovolemia as the cause of the hyponatremia, one would expect a low urine sodium. The high urine sodium means that these patients were not volume depleted, It was not loss of sodium through the sweat which lead to the low sodium. This means that changing the sodium content of sport drinks is unlikely to prevent the complication.

The authors point out NSAIDs (ibuprofen, Motrin, Advil, naproxen) enhance renal response to ADH and should be avoided in the 24-hours prior to a race.

The authors recommend treating acute symptomatic hyponatremia from a marathon with 3% saline 1 mL/kg/hr to raise serum sodium 4-6 mEq/L and then to slow the rate to target 12 mEq/L in the first 24 hours of therapy. Just as is in all cases of SIADH 0.9% saline may not improve the serum Na.