European Journal of Cardiovascular Medicine

One of the most common types of electrolyte imbalance seen in hospitalized patients is hyponatremia. In individuals who have undergone neurosurgical injury or intervention, it occurs very often. It has been demonstrated that a variety of central nervous system (CNS) related illnesses, including subarachnoid haemorrhage, traumatic brain injury, spinal cord injury, meningitis, neurosurgical operations, and many others, predispose neurosurgical patients to hyponatremia. Around 50% of patients treated for Subarachnoid Haemorrhage (SAH) and 15% to 20% of patients admitted for Traumatic Brain Injury (TBI) also experience hyponatremia [1-3]. Hyponatremia in this group must be aggressively treated since it can result in altered mental status, convulsions, vasospasm, cerebral oedema, and even death. When it happens, one of the several homeostatic processes that closely regulate serum sodium has failed [4]. Both SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion) and CSW (Cerebral Salt Wasting) are potential causes of hyponatremia in patients who have undergone neurosurgery. It may be difficult to distinguish between these two conditions in some cases because their clinical presentations overlap. The primary distinction lies in the assessment of the patient’s volume. The SIADH is characterized by a volume-expanded state, whereas CSW is characterized by a volume-contracted state. It is important to make an accurate diagnosis because treatment differs greatly between these conditions. Fluid restriction is the treatment of choice in SIADH, whereas salt and volume replacement are the treatment for CSW. Rapid changes in blood sodium offer a danger of central pontine myelinolysis, hence it is important to monitor the rate at which it is rectified [4].

This prospective cross-sectional study was conducted over one year from April 2022 to December 2022 at the Department of Neurosurgery, Nizam Institute of Medical Sciences (NIMS) Hyderabad. Inclusion in this study was voluntary and informed, and written consent was taken before enrolment. Postoperative cases of craniotomy for elective intracranial disease who developed postoperative hyponatremia were included in this study. 50 patients developed hyponatremia out of 274 patients operated for elective craniotomy in the study period. Patients with deranged renal function tests and patients who were not willing to participate in this study were excluded from this study. In patients who developed hyponatremia, serum sodium levels were sent on day 1 and were followed up for a minimum period of 3 days. Serum electrolytes were sent on the day of discharge. Serum osmolality, urine electrolytes, and urine osmolality were also sent. Treatment for hyponatremia given according to the severity of hyponatremia and type of hyponatremia. Treatment consisted of high salt diet (oral/RT feed) in 29 patients (58%), 3% NaCl in 12 patients (24%), Tolvaptan in 2 patients (2%), Mineralocorticoid in 2 patients (fludrocortisone) (2%), 3%NaCl + RT feed in 2 patients (4%), 3% NaCl + high salt diet in 1 patient (2%), 3% NaCl + Tolvaptan in 2 patients (4%) and no treatment in 2 patients. Statistical analysis was done using Microsoft Excel. Categorical data will be represented as frequencies and continuous data will be represented in the form of mean and standard deviation. p-value of <0.05 was considered significant. Pearson correlation coefficient was used to find out the correlation between continuous variables and the incidence of post-operative hyponatremia. Point bi-serial test was used to find out the correlation between categorical variables and the incidence of post-operative hyponatremia.

The mean age of the study population was 38.8 ∓ 18.57 years. The most common age group was 51-60, followed by 31-40 and 11-20 and 41-50. Males were 30 and females were 20. Average hemoglobin (Hb) of the mean population was 12.17 ∓ 2.03 grams. The mean total leukocyte count (TLC) was 10478 ∓ 3569.7 cells/cu.mm. The mean platelet counts were 2.88 ∓ 0.99 lakhs/cu.mm. The mean prothrombin time (PT) was 12.33 +/- 1.59 seconds. The mean activated partial thromboplastin time (ApTT) was 29.9 ∓ 4.53 seconds. The mean bilirubin value was 0.52 ∓ 0.32 mg/dL. The mean serum glutamic oxaloacetic transaminase (SGOT) value was 24.02 ∓ 12.16 IU/L. The mean serum glutamic pyruvic transaminase (SGPT) value was 25.15 ∓ 27.95 IU/L. The mean ALP value was 123.8 ∓ 94.85 IU/L. The mean serum protein value was 7.04 ∓ 0.56 mg/dL. The mean random blood sugar (RBS) value was 121.4 ∓ 62.1 mg/dL. The mean serum urea values were 25.22 ∓ 10.6 mg/dL. The mean serum creatinine values were 0.72 ∓ 0.22 mg/dL. The mean Initial sodium values were 135.38 ∓ 4.43 mMol/L. The mean Initial potassium values were 4.97 ∓ 4.65 mMol/L. The mean Initial chloride values were 99.48 ∓ 6.10 mMol/L.  The relationship between pre-operative investigations and post-operative hyponatremia, determined by pearson's correlation coefficient is given in the Table no. 1

Table 1: Table showing the pearsons correlation coefficient between pre-operative investigations and post-operative hyponatremia

The relationship between co-morbidities and post-operative hyponatremia done by using point biserial correlation is given in the Table no 2.

Table 2: Table showing the relationship between comorbidities and post-operative hyponatremia

The relationship between the type of tumor and post-operative hyponatremia done by using point biserial correlation is given in the Table no 3.

Table 3: The relationship between the type of tumor and post-operative hyponatremia

The diagnosis of patients is given in the table no 4.

The mean duration of 3% NaCl administration to the patients was 2.47 ∓ 0.79 days. High salt diet was given as a part of the treatment in for a mean period of 1.56 ∓ 0.6 days (Median = 1 day). Tolvaptan was given in 4 patients. The mean duration of treatment was 3.75 ∓ 1.25 days. One patient was treated with mineralocorticoids on day 4. The mean correction time for hyponatremia was 3.12 ∓ 2.9 days. The median duration for hyponatremia correction was 2 days. The mean discharge values of Na+ are 136.36 ∓ 3.02 days. The difference between pre-operative Na+ values and Na+ values at discharge is not significant at p = 0.09. The difference between POD-1 Na+ values and Na+ values at discharge is significant at p <0.00001. 32 patients underwent excision, 4 underwent clipping and 14 underwent other modes of surgery. 

Table 4: Table showing the diagnosis

Comparison of preoperative sodium values with the type of diagnosis is given in the table no 5.

Table 5: Comparison of preoperative sodium values with the type of diagnosis

Comparison of postoperative sodium values with the type of diagnosis is given in the table no. 6

Table 6: Comparison of postoperative sodium values with the type of diagnosis

Comparison of discharge sodium values with the type of diagnosis is given in the table no. 7

Table 7: Comparison of discharge sodium values with the type of diagnosis

A condition characterised by an unusually low quantity of sodium in the blood serum is referred to as hyponatremia. Both the body's overall amount of sodium in the serum's sodium concentration are subject to change independently of one another. In individuals who had chronic illnesses, hyponatremic conditions manfiest as symptomless hypotonicity, sodium depletion without water depletion, and water intoxication or dilution hyponatremia. The third and final form occurs in post-operative patients who are not "depleted" and who do not have considerable extrarenal losses of electrolytes. This is probably the most prevalent type. Post-craniotomy detection of hyponatremia is important because hyponatremia can cause symptoms and signs that are similar to those of postoperative intracranial hemorrhage. In addition, postoperative hyponatremia is typically brought on by the delivery of hypotonic fluid or the net retention of such fluid, both of which work to raise intracranial pressure and brain mass [5]. One study that was conducted retrospectively and made use of informatics demonstrated that undergoing a surgical 42 procedure was an independent risk factor for hospital-acquired hyponatremia. Plasma sodium levels tended to drop more in surgical patients than in medical patients, according to the results of a randomized controlled trial that compared 0.9% saline to 0.18% saline in a population of pediatric intensive care unit patients. The trial was conducted in a PICU [6-8]. The symptoms of encephalopathy, including seizures, obtundation, and even death, can be brought on by low serum sodium levels [8]. Post-traumatic head injury cases were not included in this study as the incidence of dyselectrolytemia is high in trauma cases, and pure neurosurgical trauma cases are rare; most trauma cases are polytrauma with other musculoskeletal, abdominal, and chest injuries.

The mean age of our study population was 38.8 ∓ 18.57 years. The most common age group was 51-60 (20%), followed by 31-40 (18%), 11-20 (16%), and 41-50 (16%). These results correlate well with Wise et al.’s study and Sousa et. al.’s study [5,9]. The Pearson correlation coefficient ratio between age and postoperative hyponatremia in our study is -0.02 (r= -0.02). The relation is very weak but negative which indicates age does not influence the onset of hyponatremia. The sex distribution of our study showed a male preponderance with 30 patients being males (60%) and 20 patients being females (40%). These results correlated well with Francis Carandang et. al.’s study on hospital-acquired hyponatremia and with Sousa et. al.’s study in which the male-to-female sex ratio was 4.8:1 [8,9]. According to the findings of many other studies, male predominance wanes with advancing years. This propensity to match the ratio between the sexes was also seen in our data, and it may be assumed that women have a longer life expectancy than males. Hyponatremia was significantly associated with longer length of stay (median 8 vs 3 days, p < 0.01), and concluded that hyponatremia was present in 25% of children after craniotomy. Preoperative hydrocephalus was an independent risk factor for hyponatremia after craniotomy.

The comorbidities of this study analyzed population included diabetes, hypertension, hypothyroidism, seizures, TB meningitis, and hepatitis B. Seizures were observed in 14% of the cases. Hypertension was observed in 12% of the cases. Diabetes mellitus was seen in 10% of the cases. Hypothyroidism and hepatitis B positivity were seen in 4% each, and TB meningitis was seen in 2% of the cases in our study. However, none of these factors showed statistical significance. Upadhyay et al.’s study concluded that patients whose blood sodium was less than 120 mmol/L had a death rate of 25%, whereas patients whose sodium levels were normal had a mortality rate of 9.3%. This indicates that the mortality rate appears to have a strong correlation with the amount of hyponatremia [4]. The mean initial serum sodium levels in our study were 135.38 mMol/L and that of post-operative levels were 131.18 mMol/L. The Pearson correlation coefficient ratio between pre-operative Sodium values and postoperative hyponatremia is 0.14 (r= 0.14). The relation is very weak but positive. Serum sodium and serum potassium levels correlated positively with post craniotomy hyponatremia whereas, serum chloride levels had a negative correlation. The mean blood urea levels of the study population in the present study were 25.22 mg/dL and the mean blood urea levels post-operatively were 22.68 mg/dL. The renal function test parameters correlated with post craniotomy hyponatremia, but with weak positivity, not statistically significant. In our study, the mean RBS levels were not correlated with post-craniotomy hyponatremia and were not significant. Serum bilirubin levels were correlated but with weak positivity, not statistically significant [4].

The Pearson correlation coefficient ratio between hemoglobin and postoperative hyponatremia is 0.64 (r=0.64). The relationship is strong and positive. We could not find similar phenomena in any of the studies in the literature. However, patients with severe anemia having hyponatremia is being reported. Hemoglobin levels, platelet counts, and aPTT levels correlated with post-operative hyponatremia whereas total leucocyte count (TLC) and Prothrombin time (PT) were negatively correlated and unrelated to post-op hyponatremia. High- or low-grade tumours, functional lesions, or vascular surgeries did not have a correlation with hyponatremia in this study. These findings in our study indicate that postoperative hyponatremia is not related to type of tumor. Hannon et al.’s review on neurosurgical hyponatremia described that a drop in plasma sodium concentrations has been described to occur following trans-sphenoidal surgery, with an incidence ranging from 3% to 25% depending on the series [2]. This is despite the fact that pituitary tumors themselves rarely cause hyponatremia, unless there is untreated glucocorticoid insufficiency present. However, this has been described as occurring [10]. SIADH is the most common cause of hyponatremia that occurs after surgery on the pituitary gland. When hypopituitarism is present before surgery, the risk of developing postoperative hyponatremia is increased [11]. Corelating the type of surgery done and post-operative hyponatremia, The cohort consisted of tumor excision in 64% of the patients. Clipping was done in 8% of the cases, and there was no difference between the type of surgery and hyponatremia. In cases of acute hyponatremia, the objective of treatment is to rapidly raise the level of sodium in the blood by between 4 and 6 mEq/L within the first one to two hours of treatment. In situations when the hyponatremia is acute or severe and patients are demonstrating neurologic abnormalities, the administration of hypertonic saline (in the form of 3% saline or 23.4% saline in more extreme cases) should be utilised as advised in studies from the literature [12]. In this study, for the number of cases with serum sodium values less than 130 mEq/l, we administered 3% NaCl. The most important complication is the possibility of developing brainstem compression due to rapidly growing cerebral edema and subsequent herniation. If sodium levels are brought back up too rapidly, especially in the presence of chronic hyponatremia, there is a risk that central pontine myelinolysis [13]. This is a risk that must be balanced against the imperative to restore normal sodium levels as soon as possible. In our study, we did not come across a single case of CPM. In some cases, oral or intravenous sodium supply using isotonic or hypertonic solutions may not be enough, especially in CSW. This is especially true for CSW patients. Pharmaceutical adjuvants, such as fludrocortisone acetate, may aid patients in these situations due to its potent mineralocorticoid properties. It enhances salt reabsorption in the renal distal tubule, perhaps combating CSW-induced natriuresis. However, some trials have shown clinical improvement in hyponatraemia, particularly in SAH patients. Fludrocortisone is currently regarded off-label for CSW therapy [4]. Recently developed vasopressin receptor antagonists have shown promise in treating SIADH in patients with euvolemic hyponatraemia. Conivaptan is the first FDA-approved ADH receptor antagonist for treating euvolemic hyponatraemia [14]. Before treating a patient with vasopressin receptor antagonists, the clinician must confirm that SIADH is the cause of hyponatraemia. This cannot be overstated. Giving conivaptan to persons with CSW would significantly worsen their volume-depleted status [2,4]. Olivia Keating et. al.’s study [15] described that hyponatremia mostly occurred on the first post-operative day, which resolved to normonatremia which was achieved in a median of 14 hours.

In the present study, the mean duration of 3% NaCl administration to the patients was 2.47 ∓ 0.79 days. High salt diet through ryle’s tube feeds were given to 2 patients of which, one patient was given RT feeds for 1 day and the other for 2 days. High salt diet was given as a part of the treatment for a mean period of 1.56 ∓ 0.6 days (median = 1 day). Tolvaptan was given in 4 patients. The mean duration of treatment was 3.75 ∓ 1.25 days. One patient was treated with mineralocorticoids on day 4. The mean correction time for hyponatremia was 3.12 ∓ 2.9 days. The median duration for hyponatremia correction was 2 days. The mean discharge values of Na+ are 136.36 ∓ 3.02 days. The difference between pre-operative Na+ values and Na+ values at discharge is not significant at p = 0.09 whereas the difference between POD 1 Na+ values and Na+ values at discharge is significant at p <0.00001 confirming the post-surgical hyponatremia. In the present study, 3% NaCl was administered to 24% of the patients. 3% NaCl along with a high-salt diet through Ryle Tube Feed was prescribed in 4% of the patients. A high-salt diet was advised in 58% of the cases and in 2% along with 3% NaCl. Tolvaptan was administered in 2% of the patients, whereas 3% NaCl with tolvaptan was administered in 4%. This study has the limitations of having a small cohort, emergency trauma cases were not included in the study and high salt diet treatment regime could not be standardized.

Hyponatremia occurs in 18.2% of electively operated craniotomy cases. Hemoglobin and serum proteins were strong influencers in the development of post-operative hyponatremia. The maximum supplement with tolvaptan was required for 2 weeks post-discharge to correct hyponatremia. Additional fludrocortisone in a single patient was required for only 4 days.

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