In the present study, we found that 16.2% of critically ill medical patients who had normal sodium concentration at the time of ICU admission developed new-onset hyponatremia within the first 48 h after admission and that net volume balance was the only modifiable factor associated with ICU-acquired hyponatremia. In addition, ICU-acquired hyponatremia patients were more likely to require RRT, although other clinical outcomes were not different between the two groups.
Contrary to our expectation that hyponatremia would be more prevalent in medical ICU patients, the incidence of ICU-acquired hyponatremia in this study was not higher compared with previous studies [4, 9,10,11]. This finding should be interpreted cautiously because we only evaluated events that developed within first 48 h, whereas previous studies investigated the entire duration of the ICU stay [4, 9,10,11]. Therefore, it would be expected that incidence would be increased if the time frame was extended.
Stelfox et al. demonstrated the inverse relationship between ICU-acquired hyponatremia and hyperkalemia as a time-dependent factor [10, 11]. Our study also indicates that ICU-acquired hyponatremia was more prevalent in patients with higher potassium concentration on ICU admission. Furthermore, the exact opposite relationship was shown between initial hypokalemia and ICU-acquired hypernatremia . These findings suggest that a single measurement of potassium concentration on ICU admission could be helpful in predicting subsequent ICU-acquired hyponatremia.
Hematologic malignancy was the only underlying condition related to the development of ICU-acquired hyponatremia. Contrary to our results, the prevalence of hematologic malignancy was lower in patients with ICU-acquired hyponatremia in the previous two studies, but there was no statistical significance [4, 9]. It is well known that hyponatremia and malignancy are closely related , and several factors were suggested as contributors to hyponatremia, including antineoplastic therapy, adrenal metastasis, and arginine vasopressin . However, these are insufficient to explain our findings because patients with pre-existing hyponatremia were excluded and patients with oncologic malignancy were evenly distributed in this study. In addition, 16.6% of our study population had hematologic malignancy, which is much higher than the proportion of hematologic malignancy in previous studies [4, 9]. This large number of patients suggests that it is not likely to be obtained by chance. Additional research is needed to ascertain the association between hematologic malignancy and ICU-acquired hyponatremia.
We investigated several management profiles to determine whether there are modifiable factors that give rise to ICU-acquired hyponatremia. We found that use of sodium bicarbonate and FFP, as well as net volume balance, were different between the 2 groups. Of these, net volume balance was the only variable of significance in multivariate analysis. This result is in agreement with the study by Steiglmair et al. showing that positive fluid balance was a single reason of ICU-acquired hyponatremia in 25% of cardiothoracic surgery patients . Interestingly, although not proven in multivariate analysis, use of sodium bicarbonate, which is an established risk factor of hypernatremia, was associated with ICU-acquired hyponatremia . It is tempting to speculate that frequent administration of sodium bicarbonate reflects metabolic acidosis in patients with acute kidney injury. This is supported by the result that patients with ICU-acquired hyponatremia were more frequently treated with RRT than normonatremia patients. The same result has been reported in patients after cardiac surgery , and new-onset hyponatremia was also related to acute kidney injury and in postoperative patients . It is uncertain whether ICU-acquired hyponatremia and renal failure coexist independently in severe patients or if ICU-acquired hyponatremia precedes manifestation of worsening renal function. Unfortunately, our data could not establish a causal relationship because of inherent limitation of observational design of the study. However, our data suggest that renal function should be closely monitored in patients with ICU-acquired hyponatremia based on the significant association between hyponatremia and renal dysfunction.
Considering the comorbidities and relative severity of illness in medical patients admitted to ICUs, limited data is available on whether ICU-acquired hyponatremia in medical ICU patients is associated with poor clinical outcomes. In the present study, clinical outcomes such as ICU mortality or LOS in patients with ICU-acquired hyponatremia was not worse compared with patients with normonatremia, inconsistent with previous reports [4, 9,10,11]. In a large retrospective study with a database of 8142 adults admitted to 3 medical-surgical ICUs consecutively over a period of 6 years , Stelfox et al. demonstrated that ICU-acquired hyponatremia and its grade were associated with increased ICU mortality. However, the proportion of medical patients included in the study was only 44%, which limits representation of clinical outcomes in medical patients with ICU-acquired hyponatremia. The other studies included surgical patients only [4, 9, 11], in which ICU mortality is relatively lower than medical patients. Therefore, further studies with a larger number of medical patients are needed to substantiate our findings.
Although this study provided new information on the factors associated with ICU-acquired hyponatremia in medical ICUs, there are several limitations that should be acknowledged. First, given the observational nature of this study, selection bias may have influenced the significance of its findings. This was addressed by adjusted multivariate analysis. However, the potential for bias due to an unmeasured confounder remains. Furthermore, the study was conducted at a single institution with a specialized ICU for critically ill cancer patients, resulting in a high proportion of cancer patients in the study, which may limit the generalizability of our findings. Second, we could not collect detailed information on type and amount of intravenous fluid, dose of each medication, and constituents and amount of nutrition therapy. These factors might have an influence on electrolyte and water imbalance, however, which could not be extracted from our data repository. Third, we only evaluated events that occurred during first 48 h, which could alter some findings. However, 50% of ICU-acquired hyponatremia developed within 2 days after admission , and confounding factors would increase as the length of the ICU stay increased. Therefore, we evaluated only events in first 48 h to evaluate modifiable risk factors during the early phase of ICU admission.