We are presented with a patient with moderate euvolemic hyponatremia, suggesting a syndrome of inadequate antidiuresis (SIAD) secondary to sertraline, although it would be necessary to have urinary osmolality to confirm this. Primary adrenal insufficiency produces hypovolemic hyponatremia (incorrect option 1). Diabetes insipidus is the opposite of this pathology, usually presenting with hypernatremia (option 4 incorrect). The question remains whether to treat aggressively with hypertonic saline, or to be more conservative by indicating hydric restriction. With natremia above 125 mmol/l it is not indicated to treat with HSS unless the patient has severe neurological symptoms, which does not seem to be the case (they describe a confusional picture that would be a moderate hyponatremic encephalopathy), and it is not indicated to restore natremia as soon as possible (due to the risk of osmotic demyelination syndrome). Therefore, the correct answer would be 3. What I do not like about this answer is that the second part ("if natraemia does not rise, switch to slow infusion of saline") is incorrect, since in this case the use of furosemide, tolvaptan or urea should be considered, not saline (and it does not indicate tonicity either, since isotonic is not the same as hypertonic). In any case, I do not see it as very likely to be overridden.

We are presented with a patient with moderate euvolemic hyponatremia, suggesting a syndrome of inadequate antidiuresis (SIAD) secondary to sertraline, although it would be necessary to have urinary osmolality to confirm this. Primary adrenal insufficiency produces hypovolemic hyponatremia ([HIDDEN]). Diabetes insipidus is the opposite of this pathology, usually presenting with hypernatremia ([HIDDEN]). The question remains whether to treat aggressively with hypertonic saline, or to be more conservative by indicating hydric restriction. With natremia above 125 mmol/l it is not indicated to treat with HSS unless the patient has severe neurological symptoms, which does not seem to be the case (they describe a confusional picture that would be a moderate hyponatremic encephalopathy), and it is not indicated to restore natremia as soon as possible (due to the risk of osmotic demyelination syndrome). Therefore, [HIDDEN]. What I do not like about this answer is that the second part ("if natraemia does not rise, switch to slow infusion of saline") is [HIDDEN], since in this case the use of furosemide, tolvaptan or urea should be considered, not saline (and it does not indicate tonicity either, since isotonic is not the same as hypertonic). In any case, I do not see it as very likely to be overridden.

A 75-year-old woman on sertraline treatment who comes to the emergency department with confusional symptoms. There is no evidence of edema and blood pressure is 130/70. The blood test shows Na 126 mEq/l and K 4 mEq/l, natriuria is 45 mEq/l and diuretic intake has been ruled out. Which of the following is the most correct approach?

It is Addison's disease and corticosteroids should be administered immediately.

Administer hypertonic saline to restore natremia as soon as possible.

Indicate water restriction and if natremia does not rise, switch to slow infusion of saline.

Request brain MRI, since it is probably diabetes insipidus.

A challenging coexistence of central diabetes insipidus and cerebral salt wasting syndrome: a case report.

Combined central diabetes insipidus and cerebral salt wasting syndrome is a rare clinical finding. However, when this happens, mortality is high due to delayed diagnosis and/or inadequate treatment. A 42-year-old white man was referred to neurosurgery due to a non-functional pituitary macroadenoma. He underwent a partial resection of the tumor on July 2, 2015. On the day following surgery he presented polyuria with sodium 149 mEq/L, plasma osmolality 301 mOsm/kg, and urine osmolality 293 mOsm/kg. He started nasal desmopressin 0.05 mg/day with good response. He was already on dexamethasone 4 mg and levothyroxine 75 mcg due to hypopituitarism after surgery. On July 9 he became confused. Cerebral computed tomography was performed with no significant changes. His natremia dropped to 128 mEq/L with development of polyuria despite maintenance of desmopressin dose. His hemoglobin and hematocrit rose from 9.1 g/L to 11.6 g/L and 27.5 to 32.5, respectively. His thyroid function was normal and he was on hydrocortisone 30 mg/day. At 12 p.m. 150 mg/hydrocortisone infusion was initiated, but sodium did not increase. Plasma and urine osmolality were 264 mOsm/kg and 679 mOsm/kg, respectively. At 4 p.m. hydrocortisone was increased and hypertonic saline replacement started. Two hours later he was dehydrated with polyuria and vomiting, and natremia of 124 mEq/L. Hyponatremia was very resistant to treatment despite hypertonic saline replacement, hence desmopressin was suspended. The following day, urine spot analysis showed that natriuresis was 63 mEq/L with serum sodium 132 mEq/L. This was interpreted as a cerebral salt wasting syndrome and control was achieved with aggressive hypertonic saline replacements and fludrocortisone 0.1 mg/three times a day. We present a rare case of a patient with diabetes insipidus and cerebral salt wasting syndrome, who was successfully treated. Hyponatremia in a patient with diabetes insipidus may erroneously be interpreted as inadequate diabetes insipidus control or as syndrome of inappropriate antidiuretic hormone secretion, leading to therapeutic errors. Thus, all clinical and analytical data should be evaluated together for early and correct diagnosis.

Severe hyponatremia due to rosiglitazone use in an elderly woman with diabetes mellitus: a rare cause of syndrome of inappropriate antidiuretic hormone secretion.

To describe the first case of syndrome of inappropriate antidiuretic hormone secretion with life-threatening hyponatremia due to rosiglitazone therapy. We describe the clinical, laboratory, and imaging findings of the study patient. An 89-year-old woman with a 5-year history of type 2 diabetes mellitus was admitted to the emergency department because of unconsciousness. She had reported generalized weakness for 15 days and nausea and vomiting for 3 days. Findings from laboratory analysis showed severe hyponatremia (sodium, 110 mEq/L). She had normal renal, cardiac, and adrenal function, and she did not have edema or volume depletion. The cause of hyponatremia was syndrome of inappropriate antidiuretic hormone secretion. We did not find any cause for her condition other than rosiglitazone, an antihyperglycemic drug that is increasingly being used in patients with type 2 diabetes mellitus. According to her medical history, rosiglitazone was prescribed 1 month previously after withdrawal of gliclazide. We stopped the rosiglitazone and administered hypertonic saline infusion to treat the hyponatremia. Saline infusion was stopped and blood sodium levels were stabilized in the normal range after 2 days. The patient's plasma sodium concentration has remained in the reference range at follow-up visits. This is the first reported case of syndrome of inappropriate antidiuretic hormone secretion as an adverse effect of rosiglitazone, and this drug should possibly be considered for addition to the list of drugs that cause this condition.

Evaluation of a protocol for hypertonic saline administration in acute euvolemic symptomatic hyponatremia: A prospective observational trial.

Acute symptomatic hyponatremia is a frequent yet poorly studied clinical problem. To develop a non-weight based protocol for the treatment of acute symptomatic hyponatremia. Observational study in a Multi-disciplinary Intensive Care Unit of an urban tertiary care hospital. Patients aged >18 years, admitted with euvolemic acute symptomatic severe hyponatremia (defined as serum sodium <120 meq/l with symptoms <24 hours), formed the study population. On confirmation of euvolemic status clinically and by laboratory investigations, patients were administered 100 ml of 3% NaCl over a period of 4 hours irrespective of the weight of the patient, followed by reassessment of serum Na at the end of 4 hours. The volume of hypertonic saline (in ml) required to increase serum Na by 8 meq/l was calculated using the formula: 100 × 8/increment in serum Na observed with 100 ml hypertonic saline. This volume was infused over the next 20 hours. To monitor renal water diuresis which may contribute to overcorrection, the urine specific gravity was monitored every 4 hours for sudden decrease of ≥ 0.010 from the baseline value. Measurement of serum Na was repeated if a fall in the urine specific gravity was observed and subsequently repeated every 4 hours. If no fall occurs in urine specific gravity, serum Na measurement was repeated at 12, 20 and at 24 hours (0 hour being the initiation of 100 ml hypertonic saline). The volume of infusate was adjusted if an excessive increment of serum Na (greater than 3 meq at 8 hours, 4 meq at 12 hours, 5 meq at 16 hours and 6 meq at 20 hours) was observed. Baseline characteristics were compared using chi-square test and Mann-Whitney U test. 58 patients formed the study cohort. The mean age was 58 years. The mean serum Na on admission was 114 meq/l. Administration of 100 ml hypertonic saline resulted in a mean increase in serum Na of 2 meq/l. The mean increase in serum Na over 24 hours was 9 meq/l and mean volume of hypertonic saline required for a serum Na increment of 8 meq/l was 600 ml. The non-weight based protocol with monitoring for water diuresis is reasonably an effective strategy in the treatment of acute euvolemic symptomatic hyponatremia.

Hyponatremia and Encephalopathy in a 55-Year-old Woman with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Isolated Presentation of SARS-CoV-2 Infection.

BACKGROUND During the coronavirus disease 2019 (COVID-19) pandemic of 2020, varied presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. The present report is of a case of hyponatremia and encephalopathy due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as the main presentation of SARS-CoV-2 infection in a 55-year-old woman. CASE REPORT A 55-year-old woman with type II diabetes mellitus presented with confusion and slurring of speech, with a temperature of 38.5°C, heart rate of 120 bpm, blood pressure of 159/81 mmHg, and oxygen saturation of 98% on room air. She did not have edema on examination. Laboratory testing showed a low sodium level of 116 mEq/L (reference range, 135-145 mEq/L) with urine osmolarity of 364 mOsm/kg, urinary sodium of 69 mEq/L, urinary potassium of 15.6 mEq/L, and serum osmolarity of 251 mOsm/kg. The patient had normal serum thyroid-stimulating hormone and cortisol levels. A chest X-ray should no pulmonary infiltrates nor did a lumbar puncture reveal signs of infection. A real-time SARS-CoV-2 polymerase chain reaction assay was positive for COVID-19. Brain imaging with computed tomography was negative for acute infarct, intracranial hemorrhage, and mass effect. Based on findings from laboratory testing and physical examination, a diagnosis of SIADH was made. The patient was treated with 3% hypertonic saline, followed by salt tablets and fluid restriction, with improvement in her clinical symptoms and serum sodium level. CONCLUSIONS The present report is of a rare but previously reported association with SARS-CoV-2 infection. Encephalopathy and hyponatremia associated with SIADH without pneumonia or other symptoms of infection should be an indication for testing for SARS-CoV-2 infection.

Syndrome of Inappropriate Antidiuretic Hormone Secretion -- Treatment / Management

Patients presenting with severe symptoms such as seizures, confusion, or delirium need urgent initial correction with hypertonic saline infusion for the first few hours rather than just water restriction. A 100 mL bolus of 3% hypertonic saline is given in the first 3 to 4 hours, and sodium levels are measured within 2 to 3 hours so that further doses can be adjusted to avoid correcting too rapidly. A rise of 3 to 4 mEq/L within the first few hours in such distressing conditions can be justified. If the patient's mental status does not improve, more boluses of 100 mL hypertonic saline can be given in the same way as above until symptoms get better.

Neurology_Adams

The desired volume of normal saline can then be determined by keeping in mind that its sodium concentration is 154 mEq/L and that of 3 percent (hypertonic) saline solution is 513 mEq/L. If hypertonic saline is administered, it is usually necessary to simultaneously reduce intravascular volume with furosemide, beginning with a dose of 0.5 mg/kg intravenously, and to increase the dosage until a diuresis is obtained. (As a rule of thumb, 300 to 500 mL of 3 percent saline, infused rapidly intravenously, will increase the serum sodium concentration by about 1 mEq/L/h for 4 h.) Guidelines to prevent an overly rapid correction of Na are elaborated further on in relation to central pontine myelinolysis (no more rapidly than 10 mmol/L in the first 24 h). Although the syndrome of SIADH is usually self-limiting, it may continue for weeks or months, depending on the type of associated brain disease.

[Hyponatremia in clinical practice].

Hyponatremia is defined as serum sodium level below 135 mEq/l; this electrolyte disorder can be associated with low, normal or high plasma tonicity. Hyponatremia with normal plasma osmolality, pseudohyponatremia, has little clinical value. Hyponatremia with increased plasma osmolality results from hyperglycemia or mannitol infusion. Patients with hyposmotic hyponatremia may be normovolemic, hypovolemic or hypervolemic; it is most important to know clinical history, physical examination that focuses on volume assessment and laboratory evaluation that includes urine osmolality and urine sodium concentration. Severe hyponatremia is associated with neurological complications and occasionally with mortality; for mild hyponatremia water restriction is usually sufficient, but in serious cases hypertonic saline infusion should be administered. Rapid correction of severe hyponatremia can cause brain demyelination; to prevent brain damage the rate of correction should be no more than 0.5 mEq/l/h (10-15 mEq/l/24 h).

Electrolyte imbalance

Treatment Considerations for treatment include symptom severity, time to onset, volume status, underlying cause, and sodium levels. If the sodium level is <120 mEq/L, the person can be treated with hypertonic saline as extremely low levels are associated with severe neurological symptoms. In non-emergent situations, it is important to correct the sodium slowly to minimize risk of osmotic demyelination syndrome. If a person has low total body water and low sodium they are typically given fluids. If a person has high total body water (such as due to heart failure or kidney disease) they may be placed on fluid restriction, salt restriction, and treated with a diuretic. If a person has a normal volume of total body water, they may be placed on fluid restriction alone.

Saline (medicine)

Hypertonic saline may be used in perioperative fluid management protocols to reduce excessive intravenous fluid infusions and lessen pulmonary complications. Hypertonic saline is used in treating hyponatremia and cerebral edema. Rapid correction of hyponatremia via hypertonic saline, or via any saline infusion > 40 mmol/L (Na+ having a valence of 1, 40 mmol/L = 40 mEq/L) greatly increases risk of central pontine myelinolysis (CPM), and so requires constant monitoring of the person's response. Water privation combined with diuretic block does not produce as much risk of CPM as saline administration does; however, it does not correct hyponatremia as rapidly as administration of hypertonic saline does. Due to hypertonicity, administration may result in phlebitis and tissue necrosis. As such, concentrations greater than 3% NaCl should normally be administered via a central venous catheter, also known as a 'central line'. Such hypertonic saline is normally available in two strengths, the

Hyperosmolar hyperglycemic state

Management Intravenous fluids Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12 liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1 L/h for the first few hours or until the condition stabilizes. Electrolyte replacement Potassium replacement is often required as the metabolic problems are corrected. It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output. Insulin Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/l, then an insulin infusion of 0.1 units/kg/hr is started. The goal for resolution is a blood glucose of less than 200 mg/dL. References

Saline (medicine)

3% NaCl has 513 mEq/L of Na and Cl. 5% NaCl has 856 mEq/L of Na and Cl. NaCl solutions that are less commonly used are 7% (1200 mEq/L) and 23.4% (approx 4000 mEq/L), both of which are used (also via central line), often in conjunction with supplementary diuretics, in the treatment of traumatic brain injury. Dextrose (glucose) 4% in 0.18% saline is used sometimes for maintenance replacement.

Dural sinus thrombosis with severe hypernatremia developing in a patient on long-term lithium therapy.

Dural sinus thrombosis has not been described in a patient with hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus. A 63-year-old man on chronic lithium therapy for schizoaffective disorder was transferred to the Emergency Department with dehydration and signs of central nervous system dysfunction after a 3-week isolation in a room in a psychiatric hospital due to exacerbation of psychiatric disorder, during which he refused to eat. Laboratory examination revealed hypertonic hypernatremia (osmolality, 359 mOsm/kg and Na, 171 mEq/L) and hyposthenuria (specific gravity, 1.010 and osmolality, 249 mOsm/kg), with normal serum endogenous vasopressin concentration (2.3 pg/mL). The serum lithium concentration was within the therapeutic range (0.94 mEq/L). Cranial computed tomography demonstrated subarachnoid hemorrhage and suggested dural sinus thrombosis. Although treatment with indomethacin (25 mg parenterally at 8-hour intervals) was somewhat effective in restoring renal concentrating capacity, he died of massive hemorrhagic infarction on the sixth hospital day, probably secondary to dural sinus thrombosis. The clinical diagnosis was confirmed by postmortem examination. Physicians should be alert for the possibility of dural sinus thrombosis as a complication of hypernatremia resulting from lithium-induced nephrogenic diabetes insipidus.

InternalMed_Harrison

The therapeutic goals in hypovolemia are to restore normovolemia and replace ongoing fluid losses. Mild hypovolemia can usually be treated with oral hydration and resumption of a normal maintenance diet. More severe hypovolemia requires intravenous hydration, tailoring the choice of solution to the underlying pathophysiology. Isotonic, “normal” saline (0.9% NaCl, 154 mM Na+) is the most appropriate resuscitation fluid for normonatremic or hyponatremic patients with severe hypovolemia; colloid solutions such as intravenous albumin are not demonstrably superior for this purpose. Hypernatremic patients should receive a hypotonic solution, 5% dextrose if there has only been water loss (as in diabetes insipidus), or hypotonic saline (1/2 or 1/4 normal saline) if there has been water and Na+-Cl– loss. Patients with bicarbonate loss and metabolic acidosis, as occur frequently in diarrhea, should receive intravenous bicar bonate, either an isotonic solution (150 meq of Na+-HCO3 in 5%

Surgery_Schwartz

of acute symp-tomatic hypernatremia. Even slower correction should be under-taken for chronic hypernatremia (0.7 mEq/h) because overly rapid correction can lead to cerebral edema and herniation. The type of fluid used depends on the severity and ease of correc-tion. Oral or enteral replacement is acceptable in most cases, or IV replacement with halfor quarter-normal saline can be used. Caution also should be exercised when using 5% dextrose in water to avoid overly rapid correction. Frequent neurologic evaluation as well as frequent evaluation of serum sodium levels also should be performed. Hypernatremia is less common than hyponatremia, but has a worse prognosis, and is an independent predictor of mortality in critical illness.29Hyponatremia Most cases of hyponatremia can be treated by free water restriction and, if severe, the administration of sodium. In patients with normal renal function, symptomatic hyponatremia usually does not occur until the serum sodium level is ≤120 mEq/L.

Syndrome of inappropriate antidiuretic hormone secretion

Diagnosis Diagnosis is based on clinical and laboratory findings of low serum osmolality and low serum sodium. Urinalysis reveals a highly concentrated urine with a high fractional excretion of sodium (high sodium urine content compared to the serum sodium). A suspected diagnosis is based on a serum sodium under 138. A confirmed diagnosis has seven elements: 1) a decreased effective serum osmolality - <275 mOsm/kg of water; 2) urinary sodium concentration high - over 40 mEq/L with adequate dietary salt intake; 3) no recent diuretic usage; 4) no signs of ECF volume depletion or excess; 5) no signs of decreased arterial blood volume - cirrhosis, nephrosis, or congestive heart failure; 6) normal adrenal and thyroid function; and 7) no evidence of hyperglycemia (diabetes mellitus), hypertriglyceridemia, or hyperproteinia (myeloma).

Neurology_Adams

Treatment of SIADH If hyponatremia has been of several days or more duration, the rapid restitution of serum sodium to normal or above-normal levels carries a risk of producing osmotic demyelination (also called central pontine myelinolysis; see Chap. 40). Our usual procedure in patients with serum sodium concentrations of 117 to 125 mEq/L is to slowly correct the sodium concentration by restricting water to 400 to 800 mL/d and to verify the desired urinary loss of water by checking the patient’s weight and serum sodium until it reaches approximately 130 mEq/L. If there is drowsiness, confusion, or seizures that cannot be confidently attributed to the underlying neurologic illness, or if the serum sodium is in the range of 100 to 115 mEq/L, isotonic or 3 percent NaCl should be infused over 3 to 4 h and furosemide 20 to 40 mg administered to prevent fluid overload. In order to avoid osmotic demyelination, a safe clinical rule is to raise the serum sodium by no more than 12 mEq/L in the

Therapeutic approach in patients with dysnatraemias.

Rapid correction of dysnatraemias is frequently associated with increased morbidity and mortality. Therefore, it is important to estimate the proper volume and type of infusate required to change the serum sodium concentration predictably. The aim of this study is to evaluate the utility or/and the accuracy of the Adrogue-Madias formula in managing patients with hyponatraemia and hypernatraemia. Among the 317 patients who either on admission to our internal medicine clinic or during their hospitalization were found to have hyponatraemia or hypernatraemia, we studied 189 patients (59.6%) in whom the administration of intravenous solutions was required for the correction of dysnatraemias. Twelve hours after starting the administration of intravenous solutions the anticipated as well as the achieved serum sodium concentration were as follows: in volume depleted patients 130.2+/-4.1 vs 131.3+/-5.2 meq/l (n = 45; P = NS), in syndrome of inappropriate antidiuretic hormone secretion (SIADH) patients 127.4+/-5.7 vs 128.9+/-5.9 meq/l (n = 10; P = NS), in patients with diuretic-induced hyponatraemia 123.8+/-6 vs 125.5+/-5.6 meq/l (n = 29; P = NS), in patients with primary polydipsia 122.5+/-0.7 vs 129+/-1.4 meq/l (n = 2; P = 0.02), while in patients with hypernatraemia 153.6+/-7.5 vs 156.5+/-8.9 meq/l (n = 92; P = 0.021). Furthermore, 24 h from the initiation of the therapeutic intervention the expected and the achieved serum sodium concentrations were 130+/-4 vs 135.6+/-3.3 meq/l (n = 15; P = 0.002) in patients with volume depletion, 128.1+/-4.8 vs 130+/-4.5 meq/l (n = 15; P = NS) in patients with diuretic-induced hyponatraemia and 151.5+/-6.4 vs 153.3+/-8.3 meq/l (n = 67; P = NS) in patients with hypernatraemia. The formula that has been proposed by Adrogue and Madias predicted with relative accuracy the changes in serum sodium concentration in almost all patients. Thus, it should be considered as a very useful tool for the management of dysnatraemias. However, special attention should be paid when this equation is used in patients with hyponatraemia due to extracellular volume depletion after euvolaemia's restoration and primary polydipsia in order to avoid rapid correction of hyponatraemia.

[Hyponatremia and hypernatremia in the elderly].

The study aimed at evaluating an incidence of hypo- and hypernatremia in the elderly and the results of therapy. Hyponatremia. The studies involved 18 patients aged 69.8 +/- 5.9 years with hyponatremia of 126.8 +/- 2.7 mmol/L. The main causes of hyponatremia were: diuretics, diarrhoea, and vomiting. Sodium deficit was calculated prior to the treatment in all patients. An analysis of hyponatremia incidence indicates that hyponatremia was diagnosed in 1.39% of patients over 60 years, hospitalized within 1989-1990. Sodium deficit in this group was 495.5 +/- 167.7 mmol. Sodium chloride solution was given intravenously to 12 patients, according to the "free correction" principle (a mean increase in serum sodium level was 0.17 +/- 0.07 mmol/L per hour). Mortality in such treated patients was 33%. Sodium chloride was not given to 6 out of examined patients. In 12 patients (66.6%) hyponatremia developed prior to hospitalization, in 6 patients (33.3%) during hospitalization. Mortality rate was 16.6% and 50%, respectively. This confirms higher mortality rate of the rapidly developing hyponatremia in the hospitalized elderly patients. In some cases hyponatremia may constitute iatrogenic complication, especially in the elderly given diuretics in an uncontrollable way. Own experience suggests that elderly patients with a risk of hyponatremia require close monitoring and early compensation of the electrolyte disorders. Hypernatremia. The studies involved 20 patients aged 71.4 +/- 7.7 years with hypernatremia of 155.6 +/- 8.4 mmol/L. A total water deficit (DH20) was calculated in this group. An analysis of hypernatremia incidence showed that this state was diagnosed in 1.55% of patients treated at the Department of Arterial Blood Hypertension within 1989-1990. Total water deficit was 3.9 +/- 1.9 L. A 5% glucose was given intravenously to 15 patients whereas oral fluid therapy was carried out in 5 patients. A mean corrected DH2O in the first day was 46.0 +/- 21.0%. Mortality rate in this group was 65%. It is worth mentioning that 37% of patients with chronic hypernatremia which developed prior to hospitalization died while in case of the acute hypernatremia developed in the hospital mortality rate was 83%. A significant effect on the results of therapy plays an early correction of hypernatremia. Mortality rate in case of DH2o supplementation below 30% during the first 24 hours is about 66%., if DH2o supplementation is 31-60%, a mortality rate is 63%, and in DH2o supplementation over 60% mortality rate is 100%. The obtained results suggest that hypernatremia in the elderly is related to the high mortality rate (65%). An early decrease of water deficit increases mortality rate in patients with hypernatremia.

Diagnosis and management of hyponatraemia in hospitalised patients.

Hyponatraemia is a commonly encountered electrolyte abnormality in hospitalised patients and is associated with significant morbidity and mortality. The fact that most cases of hyponatraemia are the result of water imbalance rather than sodium imbalance underscores the role of antidiuretic hormone (ADH) in the pathophysiology. Hyponatraemia can be classified according to the measured plasma osmolality as isotonic, hypertonic or hypotonic. Hyponatraemia with a normal plasma osmolality usually indicates pseudohyponatraemia, while hyponatraemia because of a high plasma osmolality is typically caused by hyperglycaemia. After excluding isotonic and hypertonic causes, hypotonic hyponatraemia is further classified according to the volume status of the patient as hypovolaemic, hypervolaemic or euvolaemic. Hypovolaemic hyponatraemia is accompanied by extracellular fluid (ECF) volume deficit, while hypervolaemic hyponatraemia manifests with ECF volume expansion. The syndrome of inappropriate ADH (SIADH) should be suspected in any patient with euvolaemic hyponatraemia with a urine osmolality above 100 mOsm/kg and urine sodium concentration above 40 mEq/l. In the management of any hyponatraemia regardless of the patient's volume status, it is advised to restrict free water and hypotonic fluid intake. Hypertonic saline and vasopressin antagonists can be used to correct symptomatic hyponatraemia. The rate of correction is dependent upon the duration, degree of hyponatraemia and the presence or absence of symptoms. Symptomatic acute hyponatraemia (< 48 h) is a medical emergency requiring rapid correction to prevent the worsening of brain oedema. In asymptomatic patients with chronic hyponatraemia (> 48 h or unknown duration), fluid restriction and close monitoring alone are sufficient, while a slow correction by 0.5 mEq/l/h may be attempted in symptomatic patients. Excessive rapid correction should be avoided in both acute and chronic hyponatraemia, because it can lead to irreversible neurological complications including central osmotic demyelination.

[The most frequent electrolyte disorders in the emergency department : what must be done immediately?].

Hyponatremia is the most common form of electrolyte disorder in the emergency room. The symptoms are unspecific and include nausea, dizziness and often falls. Typical symptoms of severe hypernatremia are vomiting, cerebral seizures, somnolence and even coma. The specific initial laboratory diagnostics include measurement of serum electrolytes, serum glucose, serum and urine osmolarity and sodium in urine. The main aim of the clinical examination is to estimate the volume status. If a patient has hypovolemia an infusion of isotonic sodium chloride solution (0.9 %) is the method of choice. If the patient is euvolemic the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or (neurotropic) drugs might be the cause. In these cases the primary measure is restriction of fluid intake. As a rapid correction of sodium levels can lead to pontine myelinolysis, the increase in sodium concentration must not be less than 10 mmol/l within the first 24 h and 18 mmol/l within the first 48 h. Clinical symptoms of hyperkalemia include neurological (e.g. muscle weakness, paresis, hyperreflexia, cramps and dysesthesia), gastrointestinal (e.g. nausea, vomiting and diarrhea) and cardiac symptoms (e.g. dysrhythmia and conductance disorders). Calcium injection stabilizes cardiac rhythm disorders immediately. For a rapid drop in potassium by shifting the potassium to the intracellular space, administration of glucose with insulin and high-dose inhalative administration of betamimetics can be used. Potassium elimination is achieved by infusion of isotonic sodium choride (0.9 %) with i.v. administration of furosemide, ion exchange resins and hemodialysis.

[Water intoxication following preparation for barium enema].

Induction of water intoxication from tap water enemas was reported a few years ago. Its treatment is still debated. A 4 1/2 year-old boy was admitted because he suffered from coma grade I. A barium enema had been prescribed for fecal incontinence and the patient had been given orally about 4 liters of water during the 24 hours preceding this investigation. Blood examination showed;: Na 122 mEq/l; K 3 mEq/l; Cl 87 mEq/l. Brain CT scan was normal. The patient was placed under restriction of fluid and was given i.v. 5.8% NaCl solution (2 mM/kg) for 3 hours. Convulsions appeared despite this treatment requiring intubation and ventilation plus increasing doses of NaCl: 20% solution (2 mM/kg) for 30 minutes followed by 2 mM/kg for 3 hours, associated with mannitol and furosemide infusion. Use of hypertonic saline solutions in the treatment of water intoxication is discussed. Acute hyponatremia must be rapidly corrected using hypertonic saline solution plus restriction of fluid and diuretic.

[Hyponatremia--should it be ignored or diagnosed?--Case 8/2011].

HISTORY, CLINICAL FINDINGS: A 72-year-old dehydrated female was admitted to our emergency department. She presented with a decreased level of consciousness and had experienced a fall. Her medication included hydrochlorothiazide and amiloride. Laboratory findings showed a severe hyponatremia with a serum sodium concentration of 107 mmol/l and a reduced serum osmolality. Urine sodium and potassium excretion were > 30 mmol/l. A CT scan of the head did not show any signs of trauma. Using a diagnostic algorithm, the diagnosis of a hypotonic hypovolemic hyponatremia due to the intake of diuretics was confirmed. By intravenous infusion of physiological sodium chloride solution and cessation of diuretics, serum sodium concentration was raised gradually. Hereby, the patient`s state of consciousness completely normalized. Hyponatremia represents the most frequent electrolyte disturbance of hospitalized patients. It correlates with neurological deficits, proneness to falling and intrahospital mortality. Due to diagnostic insecurity of many physicians, the finding of a hyponatremia is often ignored or misclassified. Standardized approaches using diagnostic algorithms improve diagnostic accuracy. The here presented algorithm is based on only few parameters: serum and urine osmolality, urine sodium and potassium. Besides gradual raise of serum sodium, therapy of the underlying cause is essential, for example cessation of diuretics. For patients with syndrome of inadequate secretion of antidiuretic hormone (SIADH; hypotonic isovolemic hyponatremia), selective arginin-vasopressin-receptor 2-antagonists (vaptans) are a new therapeutic option. However, due to high costs, we only see an indication for patients with SIADH who are not able to consequently comply with fluid restriction.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency

When brought to a hospital, the 1- to 3-week-old infant will be both underweight and dehydrated by appearance. Blood pressure may be low. Basic chemistries will reveal hyponatremia, with a serum Na+ typically between 105 and 125 mEq/L. Hyperkalemia in these infants can be extreme—levels of K+ above 10 mEq/L are not unusual—as can the degree of metabolic acidosis. Hypoglycemia may be present. This is termed a salt-wasting crisis and rapidly causes death if not treated. As ill as these infants can be, they respond rapidly to treatment with hydrocortisone and intravenous saline and dextrose quickly restores blood volume, blood pressure, and body sodium content, and reverses the hyperkalemia. With appropriate treatment, most infants are out of danger within 24 hours.

[Mechanism and therapy of hyponatremia with central origin].

The effect of therapy for hyponatremia with central origin (cerebrovascular disease and head injury) was investigated in order to examine contributing factors. Out of a total of 58 subjects admitted to the hospital during the previous three years with cerebrovascular disease (49 cases), and head injuries (9 cases), hyponatremia with central origin occurred within 2 weeks. Special treatment for hyponatremia was not given in 30 of the 58 cases (control group). The group (28 cases) which underwent therapy was optionally selected in terms of the following-SIADH, natriuretic polypeptide involvement and sick cells resulting from Na-K pump disorder. These 28 cases were classified into subgroups: water restricted (7 cases), hypertonic NaCl load (9 cases), glucose/insulin/potassium (GIK) therapy (4 cases), phenytoin administration (8 cases). In all of the 58 patients, the serum sodium, potassium and osmolarity and urinary sodium and potassium were measured daily. The balance of water, sodium and potassium were calculated on hyponatremic phase. Plasma levels of such hormones as antidiuretic hormone, aldosterone and cortisol were measured on hyponatremic phase. For each group, onset day and duration of hyponatremia and lowest sodium value were investigated for the sake of comparison. No significant difference for onset day and lowest sodium value was found between each group. Duration was as follows: control group 9.4 +/- 3.3 days, water restricted 7.4 +/- 2.1 days, hypertonic NaCl load 3.3 +/- 1.4 days, GIK therapy 7.3 +/- 2.9 days and phenytoin administration 8.9 +/- 3.7 days. Hypertonic NaCl load indicated a significantly shorter duration compared with the other groups. Hypertonic NaCl load was found to be most effective for hyponatremia with central origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Ringer's lactate solution

In a large-volume resuscitation over several hours, LRS maintains a more stable blood pH than normal saline. Chemistry One liter of Ringer's lactate solution contains: 130–131 mEq of sodium ion = 130 mmol L−1 109–111 mEq of chloride ion = 109 mmol L−1 28–29 mEq of lactate ion = 28 mmol L−1 4–5 mEq of potassium ion = 4 mmol L−1 2–3 mEq of calcium ion = 1.5 mmol L−1 Ringer's lactate has an osmolarity of 273 mOsm L−1 and a pH of 6.5. The lactate is metabolized into bicarbonate by the liver, which can help correct metabolic acidosis. Ringer's lactate solution alkalinizes via its consumption in the citric acid cycle, the generation of a molecule of carbon dioxide which is then excreted by the lungs. They increase the strong ion difference in solution, leading to proton consumption and an overall alkalinizing effect.

Extreme Hyponatremia Complicated by Osmotic Demyelination in a Previously Healthy Young Individual.

Severe hyponatremia can lead to dramatic complications whether it is treated or not. At times, it may be very severe (serum Na concentration: Na<subS</sub < 115 mmol/L) or even extreme (Na<subS</sub < 105 mmol/L)<supa</sup and its cause difficult to identify, especially in younger individuals with no history of water disorders. The case presented herein illustrates these points quite eloquently and leads us to believe that the current recommendations for the treatment of very severe hyponatremia require some fine-tuning. A 26-year-old man was admitted to our intensive care unit for a Na<subS</sub of 88 mmol/L in the absence of obvious extracellular fluid volume contraction. He had been experiencing vomiting, diarrhea, fatigue, and excessive thirst for the past 6 weeks and minor neurological symptoms just before admission. Laboratory tests at presentation also showed a urine osmolarity of 697 mOsm/L and urine Na of 40 mmol/L. The presenting concerns were consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH) manifesting as extreme, yet mildly symptomatic hyponatremia. At the same time, they did not point toward a specific cause initially. The patient was treated through water restriction, subcutaneous desmopressin, and various intravenous (IV) fluids. Our goal had been to increase Na<subS</sub at a rate of 4 to 6 mmol/L/day and required the amount of NaCl and free water perfused hourly to be readjusted constantly. Access to water also had to be opposed as the patient was unable to tolerate his thirst. During the first 6 days, the rate of Na<subS</sub correction achieved was ~6 mmol/L/day. The patient improved initially but at the end of day 6, he experienced severe extrapontine osmotic demyelination (with widespread pyramidal and extrapyramidal deficits) that did not respond to intravenous immunoglobulin and Na<subS</sub relowering. A little more than 3 weeks later, he began to develop low blood pressure and a subfebrile state that revealed secondary to severe Addison disease. The water disorder and insatiable thirst subsided gradually upon replacing the deficient hormones but the neurological disorder went on to become permanent and highly disabling. (1) Very severe hyponatremia should always be handled as an emergency and monitored stringently in view of its potential to cause irreparable damage. (2) Because it is a major risk factor for osmotic demyelination, it should probably be corrected at a rate of less than 4 mmol/L/day especially if it is in the extreme range, chronic, or of unknown duration. (3) It can be a presenting manifestation of Addison disease.

Simplified treatment strategies to fluid therapy in diarrhea.

Dehydration resulting from diarrhea remains an important cause of morbidity and mortality among infants and children worldwide. Although it is well established that rapid and generous intravenous restoration of extracellular fluid, followed by oral rehydration therapy (ORT) should be used in children with severe dehydration, physicians continue to be reluctant to use such therapy. Applying the principle of body fluid physiology to the current treatment of dehydration, we developed a simple and yet effective treatment strategy to fluid therapy for children with diarrheal dehydration using commercially manufactured solutions. Children with mild-to-moderate dehydration are best treated with ORT using commercially available oral solutions containing 45-75 mEq/l of Na(+). Children who have clinical evidence of severe dehydration should receive intravenous fluids, 60-100 ml/kg of 0.9% saline in the first 2-4 h to restore circulation. Oliguric patients with severe acidosis should receive a physiological dose of bicarbonate to correct blood pH level to 7.25. Once circulation is restored, the ORT should be given in small quantities to replace losses of water and Na(+) over 6-8 h. Age-appropriate diet should be started as soon as tolerated. Those who cannot tolerate ORT should receive intravenous rehydration for the remainder of the deficit and maintenance. Addition of 20 mEq/l K(+) to rehydration solutions permits repair of cellular K(+ )deficits without risk of hyperkalemia. The amount of Na(+) given to replace maintenance and deficit fluids varies with the forms of dehydration. Isonatremic dehydration is best treated with 5% dextrose in 0.45% saline containing 20 mEq/l KCl over 24 h. Hyponatremic dehydration is best treated with 0.9% saline and 0.45% saline alternately in a 1:1 ratio in 5% dextrose containing 20 mEq/l KCl over 24 h. Hypernatremic dehydration is best treated with 5% dextrose in 0.2% saline containing 20 mEq/l KCl over 2-3 days to avoid cerebral edema. Maintenance hydration is best treated with 5% dextrose in 0.2% saline containing 20 mEq/l KCl. Ideal commercial intravenous maintenance and deficit solutions have yet to appear.

A case report of syndrome of inappropriate secretion of antidiuretic hormone with marked edema due to administration of hypertonic saline.

A 61-year-old man had hyponatremia (serum Na 112 mmol/L), which was associated with disturbance of consciousness. Therefore, administration of hypertonic saline was commenced. Eventually he was diagnosed with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hypertonic saline was continued for 45 days, and plasma Na concentration rose to 138 mmol/L. At that time we were consulted regarding further administration of hypertonic saline. At the time of the consultation marked edema had developed affecting the whole body. The cardiothoracic ratio was increased and pleural effusion was evident on the chest X-ray. Administration of hypertonic saline was discontinued to prevent further worsening of the edema. Furthermore, water restriction (500 mL/day) was started. Body weight decreased by 4.3 kg in 7 days and the edema was diminished. However, plasma Na concentration decreased to 117 mmol/L. At that stage, we needed to balance the treatment of hyponatremia to the increased extracellular fluid volume (ECF). To normalize the ECF, we carried out ultrafiltration (UF) three times. Resolution of edema by using an extracorporeal UF method allowed the control of plasma Na concentration. In this case increased ECF volume hindered the adjustment of plasma Na concentration. The infusion of hypertonic saline is now used commonly by physicians. It is necessary to consider the potential risks of such treatment.

[Basic principles in liquid electrolyte treatment].

Under normal physiological conditions, our body fluids and electrolytes are protected in complete balance in a wonderful, flawless design. Even small deviations occurring in this equilibrium may lead to impairments, which can end in death. Especially in fairly common sodium metabolism disorders, it is the responsibility of the clinician to determine, according to the patient's history and her physical examination of him, whether there is an excess or depletion of volume, and to arrange subsequent treatment. Serum sodium levels of 120, 140, or 150 mEq/L alone should be meaningless to the physician in relation to total body sodium and water content because either hyponatremia or hypernatremia can occur while the patient is hypovolemic, euvolemic, or hypervolemic. For example, administering hypertonic or isotonic saline treatment to a patient with hypervolemic hyponatremia in order to correct the sodium will clinically lead to both an increase in edema and a worsening of the hyponatremia. Treatment of hypo- and hypernatremia must be adjusted separately for each patient based on his age, presence of comorbid conditions, and the speed of development of the severity of clinical signs and symptoms. Adjustments either executed too slowly or too quickly will increase mortality or morbidity. For every patient presenting unexplained symptoms of the muscular, skeletal, or neurological systems, including confusion, making the first priority the conduction of electrolyte analyses and the correctly managed effective treatment of excesses or deficiencies may save lives and will certainly save time and money that would otherwise have been spent unnecessarily.

Therapeutic relowering of the serum sodium in a patient after excessive correction of hyponatremia.

Inappropriate correction of chronic hyponatremia could lead to major neuropathological sequelae. In man, the risk of brain myelinolysis increases strikingly when correction of the serum sodium exceeds 10-15 mEq/l/24 h. No treatment is actually available for this iatrogenic brain injury. However, recent experimental data showed that rapid reinduction of the hyponatremia greatly reduces the incidence of brain damage and death in case of serum sodium overshooting. We tested this rescue manoeuver in a 71-year-old woman with nausea, confusion and severe (SNa 106 mEq/l) chronic hyponatremia related to thiazides. It was associated with hypokalemia (SK: 3.2 mEq/l). Treatment with isotonic saline produced inappropriately high SNa correction level of +21 mEq/l after the first 24 h. After initial improvement, the neurological status deteriorated after 72 h. Rapid reinduction of the hyponatremia was then ordered. Administration of hypotonic fluids (by oral and i.v. route) combined with dDAVP induced a prompt decline in the SNa (-16 mEq/l/14 h) with a final gradient of correction of deltaSNa +9 mEq/l. This manoeuver was well tolerated without untoward effects. The natremia then progressively normalized and the patient completely recovered without neurological sequelae. Hypotonic fluids may be safely administered to decrease the natremia after excessive correction of hyponatremia for potential prevention of myelinolysis.

[Clinical thinking and decision making in daily practice. An elderly man with hyponatremia].

An 88-year-old man presented with nausea and vomiting. Recently a cutaneous B-cell lymphoma had been diagnosed on his right cheek. Laboratory investigation showed hyponatraemia. Fluid restriction was started, based on the diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). However the hyponatraemia persisted and a diagnosis of 'reset osmostat' was made. CT of the abdomen revealed slight bilateral adrenal enlargement, which was interpreted as adrenal incidentaloma. No other localisation of the lymphoma, besides that on the right cheek, was seen. Although the symptoms initially disappeared, they recurred and were quickly followed by hypotension. The patient died. Post-mortem examination showed bilateral destruction of the adrenal glands due to lymphoma. The correct diagnosis was Addison's disease. This case shows that diseases do not always present with all the classical symptoms, and that it is important to consider test characteristics of diagnostic tests and to judge investigations in the context of the other clinical findings.

Myxedema -- Treatment / Management

Hypothermia should be managed with warming blankets and increasing the temperature in the room. Care in warming the patient is advised as this will cause peripheral vasodilation and may lead to hypotension and shock. As the patient receives treatment with thyroid replacement, the hypothermia will slowly resolve. Hypotension requires careful management due to multiple issues commonly present concurrently, such as hyponatremia, hypoglycemia, and hypothermia. As stated above, rapid rewarming of the patient will increase vasodilation, worsening hypotension. This action necessitates the use of fluids to maintain hemodynamic stability. If hypotension is refractory to IV fluid resuscitation, then vasopressors should be initiated until Levothyroxine has time to act. If hypoglycemia is present, 5 to 10% dextrose with half normal saline should be administered carefully. The dilemma occurs if the patient presents with hyponatremia as well. Hypotonic fluids should be avoided. Low sodium can precipitate altered mental status, and correcting the deficiency is vital. There is a careful balance between fluid restriction and the need for fluids. A central venous line is also a recommendation. [39] If hyponatremia is severe (below 120 mmol/L), careful administration of 3% sodium chloride along with intravenous bolus furosemide to allow for proper diuresis. A 4 to 6 mmol/L increase in serum sodium concentration is shown to correct many neurological symptoms. Slow correction is vital as overcorrection increases the risk for osmotic demyelination syndrome. Current research suggests that the correct rate should not increase more than 6 to 8 mmol/L in 24 hours. Once serum sodium levels rise above mmol/L, fluid restrictions should be sufficient in correcting serum sodium. [58]