Incidence and Predictors of Cerebral Salt Wasting Syndrome in Stroke Patients – Results of a Prospective Observational Study

BackgroundCerebral salt wasting syndrome (CSWS) and Syndrome of Inappropriate Anti Diuretic Hormone secretion (SIADH) are the most common aetiological factors for developing hyponatremia following stroke. The differentiation of these two entities is crucial as the treatment options are completely different. Hence the knowledge on predictors of CSWS is important to make a more accurate diagnosis of CSWS. MethodsTwo hundred and fourty six patients with confirmed stroke were prospectively observed throughout the hospital stay in a tertiary referral center in Sri Lanka to identify the possible predictors of CSWS. Hyponatremia was defined as serum Na+ level less than 131mmo/l. Serum osmolality, urine osmolality, urinary Na+, serum cortisol and thyroid function tests were performed on all the hyponatremic patients. Differentiation of the CSWS and SIADH was based on physical examination findings and laboratory parameters. ResultsThe incidence of hyponatremia in our study population was 19.1% (95% Confidence Interval 14.39-24.58). The majority of patients (24, 51%) were attributed to CSWS. SIADH group comprised of 17 (36.2%) patients and 6 (12.7%) patients had other undetermined causes. There was a significant statistical difference between the aetiologies of hyponatremia and laboratory investigations like urinary Na+, urinary osmolality and serum osmolality. Demographic characteristics, comorbidities, imaging findings and clinical parameters like systolic blood pressure, diastolic blood pressure, on admission GCS were considered in the multivariable logistic regression model and the overall model was not significant. Conclusion The incidence of CSWS is higher than the incidence of SIADH. The demographic characteristics, comorbidities, imaging and clinical parameters like blood pressure, on admission GCS could not predict the occurrence of CSWS

Evaluation of Renal Function and Plasma Osmolality among Covid-19 Patients in Sudan

Objective: COVID-19 is a very serious disease and is considered a pandemic by the WHO. The aim of this study is to determine the renal function and serum osmolality among COVID-19 patients in Khartoum state, Sudan. Method: This is retrospective study was conducted in Gebra Hospital, Khartoum state, Sudan from April 2021 to August 2021. The study enrolled 50 patients with Covid-19 and 50 healthy individuals as a control group. After all the enrolled participants signed the informed consent the samples were analyzed for Creatinine, Urea, Sodium, and potassium. By using an A25 fully automated chemistry analyzer, and serum Osmolality (mOsm / kg) was calculated according to Smithline and Gardner formula. Results: The study revealed a significant increase of the mean of Urea (P.value = 0.001), Creatinine (P.value = 0.001), however significant decrease in the mean of e GFR (P.value<0.05) on the first day of the admission. There was a significant increase in the mean of plasma Urea, Creatinine, and eGFR on the 7th day of admission when compared with the first day, P.value = (0.0001), (0.001), (0.001), respectively. The study revealed a significant difference in plasma Osmolality in COVID-19 patients (280.73 ±16.10 mOsm/kg) when compared with the control group (288.13 ±3.42 mOsm/kg), P.value = 0.0. Conclusion: COVID-19 does not affect only the lungs; it can also affect the kidney. This study concluded that there were an elevated serum creatinine, blood urea, and low glomerular filtration, and there was a significant difference in serum osmolality in COVID- 19 than in the healthy group. Keywords: COVID -19; Serum Osmolality; eGFR; Renal function; Sudan.

The Relationship between Serum Sodium, Serum Osmolality, and Intracranial Pressure in Patients with Traumatic Brain Injury Treated with Hyperosmolar Therapy

Background Treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI) is controversial. Hyperosmolar therapy is used to prevent cerebral edema in these patients. Many intensivists measure direct correlates of these agents—serum sodium and osmolality. We seek to provide context on the utility of using these measures to estimate ICP in TBI patients. Materials and Methods Patients admitted with TBI who required ICP monitoring from 2008 to 2012 were included. Intracranial pressure, serum sodium, and serum osmolality were assessed prior to hyperosmotic therapy then at 6, 12, 18, 24, 48, and 72 hours after admission. A linear regression was performed on sodium, osmolality, and ICP at baseline and serum sodium and osmolality that corresponded with ICP for 6-72-hour time points. Results 136 patients were identified. Patients with initial measures were included in the baseline analysis (n = 29). Patients who underwent a craniectomy were excluded from the 6-72-hour analysis (n = 53). Initial ICP and serum sodium were not significantly correlated (R2 .00367, P = .696). Initial ICP and serum osmolality were not significantly correlated (R2 .00734, P = .665). Intracranial pressure and serum sodium 6-72 hours after presentation were poorly correlated (R2 .104, P < .0001), as were ICP and serum osmolality at 6-72 hours after presentation (R2 .116, P < .0001). Discussion Our results indicate initial ICP is not correlated with serum sodium or osmolality suggesting these are not useful initial clinical markers for ICP estimation. The association between ICP and serum sodium and osmolality after hyperosmolar therapy was poor, thus may not be useful as surrogates for direct ICP measurements.

Nephrogenic Diabetes Insipidus with New-Onset Diabetic Ketoacidosis in a Child- Challenges in Fluid and Electrolyte Management

BackgroundIntensive care management of diabetic ketoacidosis (DKA) is targeted to reverse ketoacidosis, replace the fluid deficit, and correct electrolyte imbalances. Adequate restoration of circulation and treatment of shock is key. Pediatric treatment guidelines of DKA have become standard but complexities arise in children with co-morbidities. Congenital nephrogenic diabetes insipidus (NDI) is a rare hereditary disorder characterized by impaired renal concentrating ability and treatment is challenging. NDI and DKA together have only been previously reported in one patient.Case Diagnosis/TreatmentWe present the case of a 12-year-old male with NDI and new onset DKA with hyperosmolality. He presented in hypovolemic shock with altered mental status. Rehydration was challenging and isotonic fluid resuscitation resulted in increased urine output and worsening hyperosmolar state. Use of hypotonic fluid and insulin infusion led to lowering of serum osmolality faster than desired and increased the risk for cerebral edema. Despite the rapid decline in serum osmolality his mental status improved so we allowed him to drink free water mixed with potassium phosphorous every hour to match his urinary output (1:1 replacement) and continued 0.45% sodium chloride based on his fluid deficit and replacement rate with improvement in his clinical status.ConclusionsThis case illustrates the challenges of managing hypovolemic shock, hyperosmolality, and extreme electrolyte derangements driven by NDI and DKA.

Association Between Serum Osmolality and Acute Kidney Injury in Critically Ill Patients: A Retrospective Cohort Study

Purposes: Acute kidney injury (AKI) is a common complication in critically ill patients and is usually associated with poor outcomes. Serum osmolality has been validated in predicting critically ill patient mortality. However, data about the association between serum osmolality and AKI is still lacking in ICU. Therefore, the purpose of the present study was to investigate the association between early serum osmolality and the development of AKI in critically ill patients.Methods: The present study was a retrospective cohort analysis based on the medical information mart for intensive care III (MIMIC-III) database. 20,160 patients were involved in this study and divided into six subgroups according to causes for ICU admission. The primary outcome was the incidence of AKI after ICU admission. The association between early serum osmolality and AKI was explored using univariate and multivariate logistic regression analyses.Results: The normal range of serum osmolality was 285–300 mmol/L. High serum osmolality was defined as serum osmolality &gt;300 mmol/L and low serum osmolality was defined as serum osmolality &lt;285 mmol/L. Multivariate logistic regression indicated that high serum osmolality was independently associated with increased development of AKI with OR = 1.198 (95% CL = 1.199–1.479, P &lt; 0.001) and low serum osmolality was also independently associated with increased development of AKI with OR = 1.332 (95% CL = 1.199–1.479, P &lt; 0.001), compared with normal serum osmolality, respectively.Conclusions: In critically ill patients, early high serum osmolality and low serum osmolality were both independently associated with an increased risk of development of AKI.

Comparison of 1.0 g/kg of 20% mannitol initiated at different time points and effects on brain relaxation in patients with midline shift undergoing supratentorial tumor resection: a randomized controlled trial

OBJECTIVE Previous studies have suggested the use of 1.0 g/kg of 20% mannitol at the time of skin incision during neurosurgery in order to improve brain relaxation. However, the incidence of brain swelling upon dural opening is still high with this dose. In the present study, the authors sought to determine a better timing for mannitol infusion. METHODS One hundred patients with midline shift who were undergoing elective supratentorial tumor resection were randomly assigned to receive early (immediately after anesthesia induction) or routine (at the time of skin incision) administration of 1.0 g/kg body weight of 20% mannitol. The primary outcome was the 4-point brain relaxation score (BRS) immediately after dural opening (1, perfectly relaxed; 2, satisfactorily relaxed; 3, firm brain; and 4, bulging brain). The secondary outcomes included subdural intracranial pressure (ICP) measured immediately before dural opening; serum osmolality and osmole gap (OG) measured immediately before mannitol infusion (T0) and at the time of dural opening (TD); changes in serum electrolytes, lactate, and hemodynamic parameters at T0 and 30, 60, 90, and 120 minutes thereafter; and fluid balance at TD. RESULTS The time from the start of mannitol administration to dural opening was significantly longer in the early administration group than in the routine administration group (median 66 [IQR 55–75] vs 40 [IQR 38–45] minutes, p < 0.001). The BRS (score 1/2/3/4, n = 14/26/9/1 vs 3/25/18/4, p = 0.001) was better and the subdural ICP (median 5 [IQR 3–6] vs 7 [IQR 5–10] mm Hg, p < 0.001) was significantly lower in the early administration group than in the routine administration group. Serum osmolality and OG increased significantly at TD compared to levels at T0 in both groups (all p < 0.001). Intergroup comparison showed that serum osmolality and OG at TD were significantly higher in the routine administration group (p < 0.001 and = 0.002, respectively). Patients who had received early administration of mannitol had more urine output (p = 0.001) and less positive fluid balance (p < 0.001) at TD. Hemodynamic parameters, serum lactate concentrations, and incidences of electrolyte disturbances were comparable between the two groups. CONCLUSIONS Prolonging the time interval between the start of mannitol infusion and dural incision from approximately 40 to 66 minutes can improve brain relaxation and decrease subdural ICP in elective supratentorial tumor resection.

Effects of Daytime Dry Fasting on Hydration, Glucose Metabolism and Circadian Phase: A Prospective Exploratory Cohort Study in Bahá'í Volunteers

Background: Religiously motivated Bahá'í fasting (BF) is a form of intermittent dry fasting celebrated by abstaining from food and drinks during daylight hours every year in March for 19 consecutive days.Aim: To test the safety and effects of BF on hydration, metabolism, and the circadian clock.Methods: Thirty-four healthy Bahá'í volunteers (15 women) participated in this prospective, exploratory cohort study. Laboratory examinations were carried out in four study visits: before fasting (V0), in the third week of fasting (V1) as well as 3 weeks (V3) and 3 months (V4) after fasting. Data collection included blood and urine samples, anthropometric measurements and bioelectrical impedance analysis. At V0 and V1, 24- and 12-hour urine and serum osmolality were measured. At V0–V2, alterations in the circadian clock phase were monitored in 16 participants. Our study was augmented by an additional survey with 144 healthy Bahá'í volunteers filling out questionnaires and with subgroups attending metabolic measurements (n = 11) and qualitative interviews (n = 13), the results of which will be published separately.Results: Exploratory data analysis revealed that serum osmolality (n = 34, p &lt; 0.001) and 24-hour urine osmolality (n = 34, p = 0.003) decreased during daytime fasting but remained largely within the physiological range and returned to pre-fasting levels during night hours. BMI (body mass index), total body fat mass, and resting metabolic rate decreased during fasting (n = 34, p &lt; 0.001), while body cell mass and body water appeared unchanged. The circadian phase estimated by transcript biomarkers of blood monocytes advanced by 1.1 h (n = 16, p &lt; 0.005) during fasting and returned to pre-fasting values 3 weeks after fasting. Most observed changes were not detectable anymore 3 months after fasting.Conclusions: Results indicate that BF (Bahá'í fasting) is safe, has no negative effects on hydration, can improve fat metabolism and can cause transient phase shifts of circadian rhythms.Trial Registration:https://www.clinicaltrials.gov/, identifier: NCT03443739.

Patient-Specific Risk Factors Associated With the Development of Hyperchloremia in a Neurocritical Care Intensive Care Unit

Background: Hypertonic sodium chloride (HTS) is used in intensive care unit (ICU) settings to manage cerebral edema, intracranial hypertension, and for the treatment of severe hyponatremia. It has been associated with an increased incidence of hyperchloremia; however, there is limited literature focusing on hyperchloremic risk in neurologically injured patients. Objective: The primary objective of this study was to determine risk factors associated with development of hyperchloremia in a neurocritical care (NCC) ICU population. Methods: This was a retrospective case-control study performed in an adult NCC ICU and included patients receiving HTS. The primary outcome was to evaluate patient characteristics and treatments associated with hyperchloremia. Secondary outcomes included acute kidney injury and mortality. Results: Overall, 133 patients were identified; patients who were hyperchloremic were considered cases (n = 100) and patients without hyperchloremia were considered controls (n = 33). Characteristics and treatments were evaluated with univariate analysis and a logistic regression model. In the multivariate model, APACHE II Score, initial serum osmolality, total 3% saline volume, and total 23.4% saline volume were significant predictors for hyperchloremia. In addition, patients with a serum chloride greater than 113.5 mEq/L were found to have a higher risk of acute kidney injury (AKI) (adjusted OR 3.15; 95% CI 1.10-9.04). Conclusions: This study demonstrated APACHE II Score, initial serum osmolality, and total 3% and 23.4% saline volumes were associated with developing hyperchloremia in the NCC ICU. In addition, hyperchloremia is associated with an increased risk of AKI.

What Does SGLT2 Inhibition Add in Managing Hyponatremia Secondary to Syndrome of Inappropriate Antidiuresis (SIAD)?

Background: Apart from treating the underlying causes, other treatment options for SIAD are of limited success. Drug repurposing of SGLT2 inhibitors for use in SIAD has been suggested. Clinical Case: A 72 years old gentleman with type 2 diabetes mellitus, hypertension, ischemic cardiomyopathy (ejection fraction 40%) and paranoid personality disorder presented with 3-day history of confusion, vomiting and reduced appetite. On examination, he was fully alert, afebrile, blood pressure 173/81 mmHg, heart rate 83 beats per minute and euvolemic. There were fine crackles in the lung bases bilaterally. Random capillary blood glucose level was 5.6 mmol/L (100 mg/dL) and there was no hypoxia. Laboratory results were suggestive of SIAD (serum sodium [Na] 115 mmol/L, serum osmolality 241 mmol/kg, urine osmolarity 458 mmol/kg, spot urine Na 56.7 mmol/L) with normal fT4 (17.6 pmol/L [1.37 ng/dL]), TSH (1.6 mIU/L) and cortisol (821 nmol/L [29.7 mcg/dL]) levels. Medications at admission were daily dosing of olanzapine 7.5 mg, sitagliptin/metformin 50/850 mg, losartan 50 mg, rosuvastatin 10 mg and aspirin 100 mg. Further investigations for causes of SIAD including magnetic resonance imaging of the brain and contrast-enhanced computed tomography of thorax, abdomen and pelvis were normal. He was treated with fluid restriction (1 liter/day) and furosemide (oral 20 mg daily for 2 doses, followed by intravenous 20 mg twice daily for 3 doses) on day 1-4, leading to negative fluid balance (total 3300 ml) with an increment in serum Na to 124 mmol/L on day 5. However, this was accompanied by a reduction in systolic blood pressure (148 to 118 mmHg) and serum potassium level (4.7 to 3.7 mmol/L), along with marked increases in urea (2.7 to 8.8 mmol/L) and creatinine levels (51 to 75 µmol/L) (eGFR from &gt;90 to 87 mL/min/1.73m2). Hence, furosemide was stopped and empagliflozin 12.5 mg daily was initiated on day 5 with continuation of fluid restriction. Serum Na level increased by 2 mmol/L to 126 mmol/L after 12 hours and by 3 mmol/L (to 129 mmol/L) on subsequent day with negative fluid balance (950 ml per 24 hours). Urea and eGFR levels improved and losartan was reintroduced for blood pressure control. There was no euglycemic diabetic ketoacidosis episode. Patient was discharged on day 10 with a serum Na level of 131 mmol/L. Outpatient follow up 5 days after discharge showed further improvement in serum Na level to 134 mmol/L with serum osmolality 286 mmol/kg and urine osmolarity 672 mmol/kg. Clinical Lesson: SGLT2 inhibition can be considered as one of the treatment options of hyponatremia secondary to SIAD with good tolerability