This is the first study from this country, reported the sodium disorder in Covid − 19 patients admitted in Covid-19 facility at Indus Hospital Karachi.
This study showed that the higher age, HTN, DM, IHD, AKI, TEE and Hypovolemia had devastating impact on sodium balance. We found that hyponatremia was more prevalent than hypernatremia 23%vs 12.1%, but hypernatremia has catastrophic effect on patient’s survival as compared with hyponatremia. There are reason for it, as we know that higher age impairs water metabolism, there is relative as well as absolute reduction in total body water, which makes elderly population distinctly inclined to developed dysnatremias (10). Ageing, not only impair the thirst mechanism (11), but it also reduce the concentrating capability of kidneys which increases the risk of dehydration and hypernatremia (12).On the other hand their ability to excrete water load is also hamper, this predisposition contributes to the commonly observed episode of hyponatremia in elderly hospitalized patients who received hypotonic fluid without proper monitoring (13).
We found significantly higher number of DM patients with both conditions in our population like other study in which, DM is a well-known cause of dysnatremias (14). In an another study of 113 patients Liamis et al found poorly controlled sugar level was the major factor in the development of hypernatremia in one third (34%) of their patients. The possible explanation of this observation is the glycosuria induced osmotic diuresis, which tends to raise the serum sodium levels. Steroids are the mainstay of covid 19 therapy, which has dual effect on the generation of hypernatremia, steroids tends to raise the blood sugar level and make it difficult to control, causes osmotic diuresis, concomitantly, they have mineralocorticoid activity which retain sodium and causes hypernatremia. Similarly, hyponatremia can also develop in DM patients by various mechanisms. Firstly, hyperglycemia causes water shift from intracellular to extracellular space causes translocational hyponatremia. Secondly, excessive thirst causes increase water intake and in the background of covid pneumonia, an increase surge of antidiuretic hormone can cause hyponatremia. (15).
In our study, hypertension was significantly associated with hypernatremia, although hyponatremia was also common but didn’t reach to a significant level. Ruiz and Cuesta in HOPE-COVID-19 registry analysis also found significant association of hypernatremia in hypertensive patients, the mechanism of this finding is not evident and it will need further evaluation (16). The hyponatremia on the other hand is also reportedly associated with covid hypertensive patients. The underlying mechanism is supposed to be an increased proinflammatory cytokine release like interleukin (IL)-6 induces antidiuretic hormone (ADH) production by direct non osmotic stimulation of ADH. Indirect stimulation of IL-6 is mediated by an injury to the alveolar basement membrane, resulting in activation of hypoxic pulmonary vasoconstriction pathway that lead ADH release61 (17).On the contrary, IHD was significantly associated with hyponatremia than hypernatremia. This association is also reported in HOPE –COVID-19 registry (16)
In our population, sodium metabolism was affected by the complications of covid-19 infection, like AKI and TEE. We found that, the patients who had AKI developed hypernatremia 5.5 times more as compared to those who did not have AKI. Sjöström and Rysz examined the value of sodium as a prognostic marker for length of hospitalization, AKI and mortality in a cohort of 223 critically ill patients with covid 19. They found patients who developed AKI developed severe hypernatremia along with high mortality (18). Similarly, TEE are well known complication of Covid 19 infection and we found this complication in those who have hypernatremia. The underlying pathophysiology of this macro and micro thrombi in small vessels is not clear and it needs further study (19). Multiple small studies in which critically ill patients with COVID-19 were routinely screened for thrombotic disease demonstrated high rates of thrombotic complications in these patients ranging from 69–85% despite thrombo prophylaxis (20, 21, 22).Similar to this we also observed hypernatremia leaded to critical illness like need of vasopressor and ventilatory support and high mortality. In a case series of covid patients with hypernatremia Zimmer et al found similar observation of increased ventilatory support along with increased ICU stay (5). On the other hand we didn’t find any significant effect of hyponatremia on severity of disease. However in a registry analysis Sanchez et al found hyponatremia as an independent risk factor for an increase in mortality as well as for an increase in the development of sepsis and requirement for intensive therapy. The reason of their finding might be due to relatively larger sample size of their study (16).
In conclusion, we found dysnatremias are frequent feature of covid 19 infection. The risk factors for this are older age, comorbid conditions and development of complications. Among the dysnatremias, hypernatremia had distressing impact on severity of disease and outcome.