What is it about?
In amyotrophic lateral sclerosis (ALS), the muscles for breathing become weak. Because of this, carbon dioxide (CO₂) slowly increases in the blood. This often happens before the patient notices breathing symptoms. Early detection is important, because it helps to decide the timing of non-invasive ventilation (NPPV). NPPV can prolong survival and improve quality of life. The standard test for CO₂ is arterial blood gas analysis. However, this test is invasive, so it is not easy to repeat at every clinic visit. In this study, we examined 88 ALS patients (116 blood samples). We focused on the Na-Cl value, which is the difference between sodium and chloride. It can be calculated from routine blood tests, with no extra cost. We found that the Na-Cl value correlated well with CO₂ (PCO₂, r = 0.71) and with bicarbonate (r = 0.78). The reason is as follows. When CO₂ increases, the kidney keeps more bicarbonate to compensate, and as a result the Na-Cl value becomes larger. A Na-Cl value of 37 mEq/L or more detected CO₂ retention with high sensitivity (85%). A value of 39 mEq/L or more was highly specific (93%). The result was almost the same in limb-onset and bulbar-onset patients.
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Why is it important?
Sodium and chloride are measured in almost all routine blood tests. Therefore, we can screen for CO₂ retention without any additional test or cost. This is useful even when sodium and chloride are each within the normal range. We propose a simple two-step use: 37 mEq/L or more to suspect CO₂ retention, and 39 mEq/L or more to suspect it strongly and to confirm by blood gas analysis. This method may help to find breathing problems earlier, and to not miss the timing of ventilation. It is especially helpful when blood gas or bicarbonate is not measured routinely. However, the Na-Cl value can also increase for other reasons, such as diuretics or a high anion gap. So these conditions should be checked first.
Perspectives
In daily practice, it is often difficult to decide the right time to start ventilation in ALS. Some patients have few symptoms, but their CO₂ is already high. This problem was the reason for our study. I was glad to find that a value from routine blood tests can help to detect this early. Our study is retrospective and from a single center. So the next step is a prospective study to confirm the cutoff values. We also plan a longitudinal study, to follow patients over time and to see how the Na-Cl value changes as respiratory function declines. I hope this simple marker can support earlier and better-timed respiratory care for ALS patients.
Isamu Yamakawa
Shiga Ika Daigaku
Read the Original
This page is a summary of: Serum Na-Cl value from routine blood tests reflects CO2 retention in amyotrophic lateral sclerosis, PLOS One, September 2026, PLOS,
DOI: 10.1371/journal.pone.0358772.
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