Review of Drug-Induced Hyponatremia (Am J Kid Dis 2008;52:144)
treatment of chronic hyponatremia
from C L E V E L A N D C L I N I C J O U R N A L O F ME D I C I N E V O L UME 7 7 N UMB E R 1 0 O C T O B E R 2 0 1 0
Stern Review and Case Example (severe hyponatremia requiring ddavp)
if you overcorrect, consider dDAVP 1-2 mcg and possibly D5W 6ml/kg (see here and here)
hypokalemia repletion will raise the sodium
Sodium<135 mEq/L, <120 is severe
See diabetic section for correction in hyperglycemia
caused by non-osmotic secretion of AVP in over 95% of cases
Hypothalamic osmo-receptors. A decrease in osm of 1-2% stops AVP secretion and we pee water
Non-osmotic is mediated by arterial stretch baroreceptors in response to 8-10% decrease in blood pressure
If the kidney is damaged acutely or chronically, FeNa may not be <1 even in volume depletion
only hypovolemic hyponatremia should be treated with NS (FeNa <1), but SIADH pts can become volume depleted
50 ml of 3% should increase Na by ~1 mmol/L
In hypovolemic hyponatremia, there is a deficit of both total body water and sodium, but relatively less deficit of water, thus causing hyponatremia. A history of vomiting, diarrhea, diuretic use, or hyperglycemia with glucosuria, along with increased thirst, weight loss, orthostatic hypotension and tachycardia, and dry mucous membranes, supports the diagnosis of hypovolemic hyponatremia. If the fluid and sodium losses are extrarenal, such as gastrointestinal losses, FENa should be less than 1%. On the contrary, if the source of sodium and water losses is the kidney, for example, diuretics, glucosuria, or bicarbonaturia, then FENa will be greater than 1% .
In euvolemic hyponatremia, total body sodium concentration is near normal so there should be no evidence of ECFV depletion or excess, that is, no peripheral edema, ascites, pulmonary congestion, or pleural effusions. Before turning to the diagnosis of SIADH in patients with euvolemic hyponatremia, several other clinical entities need to be excluded. These include hypothyroidism (measure thyroid-stimulating hormone), hypopituitarism (measure cortisol response to adrenocorticotropic hormone), severe emotional (e.g. psychosis) or physical stress (e.g. anesthesia and surgery), and various medications that stimulate antidiuretic hormone (ADH) release. There are various pharmacological agents associated with SIADH:
1. Nicotine,2. Chlorpropamide,3. Tolbutamide,4. Clofibrate,5. Cyclophosphamide,6. Morphine,7. Barbiturates,8. Vincristine,9. Carbamazepine (Tegretol),10. Acetaminophen,11. NSAIDs12. Antipsychotics,13. Antidepressants.
In the absence of these diagnoses, SIADH can be entertained, and a search for pulmonary or central nervous system infections, vascular, or neoplastic diseases should reveal the cause in over 90% of SIADH cases. Because the urine volume in SIADH is low, for example, 500 ml/24 h, the urinary sodium concentration is generally high even when the patient is in sodium balance. For example, with a very modest daily sodium intake of 100 mmol/24 h, the urinary sodium concentration in 500 ml of daily urine would have to be 200 mmol/l of urine for the patient to remain in sodium balance. Thus, a high urine sodium concentration in SIADH should not be called renal sodium wasting.
In hypervolemic hyponatremia, total body sodium concentration and water are increased, but total body water is increased more, and thus hyponatremia occurs. When hypervolemic hyponatremia occurs with cardiac failure or cirrhosis, the patient has advanced and, therefore, readily diagnosed disease. Decreased plasma sodium concentration is a risk factor for poor survival in patients with cardiac failure and cirrhosis . In the absence of diuretics, FENa should be below 1.0% in hyponatremic cardiac or cirrhotic patients, as the kidney is normal and responding to decreased arterial perfusion in these edematous disorders. Specifically, in case of either a successful heart or liver transplant in cardiac or hepatic failure patients, respectively, the kidneys no longer retain sodium and water. The situation in which hypervolemic hyponatremia occurs with a FENa greater than 1.0% is with acute kidney injury or chronic kidney disease, settings in which renal tubular dysfunction is present and neither water nor sodium can be optimally excreted.
do not use conivaptan in cirrhotic/esoph varices pts
new term is osmotic demyelination
for fluid restriction, must be less than output+insensible losses
average daily insensible ~250 cc
demeclocycline 600-1200 mg/day in divided doses
increase dose only every 3-4 days
causes nephrogenic DI
shift into cells. Thiazide-induced hyponatremia occurs most commonly in elderly women, and there is also some evidence that the predisposed women may be drinking more water than normal. One limitation of the urinary excretion of electrolyte-fee water is the amount of solute excreted. With maximal urinary dilution of 50 mmol/l and diminished daily solute intake of 200 mmol/l, only 4 l of electrolyte-free water can be excreted. This is the problem that causes hyponatremia with beer drinkers who are not eating. Beer is very hypotonic and contains little solute; therefore, these beer drinkers may develop hyponatremia with an intake of 610 l of beer/day. Normal solute intake is 600800 mmol/day, thus allowing for substantial electrolyte-free water excretion.
With more individuals involved in prolonged and strenuous physical exercise such as marathons, ultramarathons, and triathlons, the entity of exercise-associated hyponatremia has emerged. Risk factors for these individuals include low body mass, less well trained, race time exceeding 4 h, consumption of fluids every mile, and the use of NSAIDs . The occurrence of exercise-induced hyponatremia does not seem to be due to sodium imbalance, but rather due to retention of more water. With such vigorous exercise, the nonosmotic stimulation of AVP would be expected, thereby leading to renal water retention [45,46]. When hypotonic fluid ingestion exceeds insensible loss due to sweating, the runner actually gains weight and hyponatremia occurs. The symptomatic hyponatremic runners generally have ingested amounts of hypotonic fluid, for example, water or Gatorade, in excess of 400800 ml/h. They may develop seizures, ataxia, disturbed level of consciousness, focal neurological deficits, and even mortality can occur. In runners with these symptoms, treatment with 3% hypertonic saline should begin immediately, even before the measurements of serum sodium concentration have returned, and continued until symptoms resolve. Further treatment is generally not needed when serum sodium concentration reaches 130 mmo/l.
hyperlipidemia, hyperproteinemia, or the absorption of isotonic glycine during transurethral resection of the bladder or prostate
hyperglycemia or the administration of hypertonic mannitol: induce osmotic water movement out of the cells and lower the plasma sodium concentration by dilution
Hypotonic Hyponatremia=true hyponatremia
(<285 on Osm)
CHF, Hepatic (UNA<20) Nephrotic (UNa>20)
SIADH (fluid restriction, Lithium blocks action of ADH),
Urine Specific Grav Elevated, Uosm>SerumOsm, Urine Na>18 (elevated),
Pyschogenic Polydipsia (Uosm<100), Endocrine (Hypothyroid, Addison’s)
Will usually have a urine sodium>20 mEq/L
vomiting, diarrhea(UNa<20), diuretics and adrenal insufficiency (UNa>20), RTA
The use of electrolyte free irrigation fluid during prostate surgery (TURP) or endometrial ablation has also resulted in hyponatremia
The hyponatremic state leads to cerebral edema, if chronic, solute loss will allow equilibrium
If corrected too quickly, get Central Pontine Myelosis
RX: Obtain UA, U Lytes, and Uosm. If symptomatic, give 100 cc of 3% Saline along with 10-20 mg of Lasix. Recheck Sodium. If it has not gone up 2 meq/L repeat 3% saline. Correct .5 meq/L per hour for non-symptomatic. Raise 1-2 meq/L per hour for symptomatic. Switch to saline after raising sodium the first couple of points.
Change in Serum Na from 1 liter of NS=(154 pts Na) / (1 + (0.5 x weight in Kg))
Change in Serum Na from 1 liter of 3% Saline=(513 pts Na) / (1 + (0.5 x weight))
Best Review Article: (NEJM 342:21, 2000)
From: Thomas Bleck <email@example.com> Date: May 7, 2008 6:49 PM The degree of hypo-osmolality is not as important as the rate at which it develops. If this is acute (over hours), then coma and (usually generalized) seizures are a consequence of the rapid drop in osmolality with a concomitant increase in ICP due to brain swelling. If it developed over days or weeks, then the brain loses solute to compensate and doesn’t swell. Most drug-induced hypo-osmolality is chronic, although if such a patient (or one with SIADH) drinks a lot of free water the osmolality may fall precipitously. The low urine osmolality would be more compatible with water intoxication than pure drug effect or SIADH, in which the urine should be inappropriately concentrated.
“beer” potomania syndrome: no solutes from poor nutrition. Free water is retained.
new drug for SIADH
promotes pure aquaresis, 6 meq rise in Na per liter
Cerebral Salt Wasting
Cerebral Salt Wasting Characteristics
- Onset within first week of CNS insult
- Duration usually 2 – 4 weeks (may be longer)
- Serum [Na+] < 130 meq/l (if permitted to fall)
- Urine [Na+] > 80 meq/l
- Urine/plasma osmolality ratio > 1 (usually > 2)
- Negative water and salt balance
Treat with NS and salt tablets 2-4 g PO q4-8 hours; extreme cases may need 3% Saline at 50 ml/hr and up. Can also use fludrocortisone 0.05-0.2 mg PO QD to promote distal sodium absorption. After hyponatremia is corrected, uric acid may differentiate CSW and SIADH.
Tests: Urine osmolality
In those patients with hyponatremia and a low plasma osmolality, the urine osmolality can be used to distinguish between impaired water excretion (which is present in almost all cases) and primary polydipsia, in which water excretion is normal but intake is so high that it exceeds excretory capacity. The normal response to hyponatremia (which is maintained in primary polydipsia) is to completely suppress ADH secretion, resulting in the excretion of a maximally dilute urine with an osmolality below 100 mosmol/kg and a specific gravity 1.003. Values above this level indicate an inability to normally excrete free water that is generally due to continued secretion of ADH. Most hyponatremic patients have a relatively marked impairment in urinary dilution that is sufficient to maintain the urine osmolality at 300 mosmol/kg or greater. There are two hyponatremic disorders other than primary polydipsia in which the urine osmolality may be below 100 mosmol/kg: Malnutrition, often in beer drinkers, in which dietary solute intake (sodium, potassium, protein) and therefore solute excretion is so low that the rate of water excretion is markedly diminished even though urinary dilution is intact.
Reset osmostat after a water load appropriately suppresses ADH release. The major clinical clue to the presence of this disorder is a moderately reduced plasma sodium concentration (usually between 125 and 135 meq/L) that is stable on multiple measurements. (See “Treatment of hyponatremia: SIADH and reset osmostat”, section on Reset osmostat).
Urine sodium concentration
In the absence of adrenal insufficiency or hypothyroidism, the two major causes of hyponatremia, hypoosmolality, and an inappropriately concentrated urine are one of the causes of effective volume depletion or of the SIADH . (See “Causes of the SIADH”). These disorders can usually be distinguished by measuring the urine sodium concentration which is typically below 25 meq/L with hypovolemia (unless there is renal salt-wasting, due most often to diuretic therapy, or cerebral salt-wasting) and above 40 meq/L in patients with the SIADH who are normovolemic and whose rate of sodium excretion is determined by sodium intake [5-7]. In addition to the initial value, serial monitoring of the urine sodium concentration may be helpful in selected cases in which the correct diagnosis may not be apparent. Suppose, for example, that the urine sodium concentration falls from 50 to 10 meq/L following the administration of 1 to 2 liters of isotonic saline. Surreptitious thiazide diuretic ingestion should be suspected in this setting. The urine sodium concentration was elevated on the first measurement because of the action of the diuretic. Once this wore off, the true state of volume depletion was unmasked even though the patient had been partially rehydrated. (See “Diuretic-induced hyponatremia”). As another example, suppose that the initial urine sodium concentration is 5 meq/L, suggesting hyponatremia due to effective volume depletion. If this were the only problem, then fluid repletion should lead to the excretion of a dilute urine (due to elimination of hypovolemic stimulus to ADH release) and rapid correction of the hyponatremia. If, however, the urine sodium concentration rises to above 40 meq/L and the urine osmolality remains above 100 mosmol/kg, then the patient also has the SIADH.
To summarize, hyponatremia due to the SIADH is characterized by the following set of findings:
- A fall in the plasma osmolality
- An inappropriately elevated urine osmolality (above 100 mosmol/kg and usually above 300 mosmol/kg)
- A urine sodium concentration usually above 40 meq/L
- A relatively normal plasma creatinine concentration
- Normal acid-base and potassium balance (see below)
- Normal adrenal and thyroid function.
Treatment of hyponatremia: SIADH and reset osmostat (Burton D Rose, MD) INTRODUCTION Hyponatremia in the syndrome of inappropriate antidiuretic hormone secretion (SIADH) results from ADH-induced retention of ingested or infused water. Appropriate therapy in this disorder is dependent upon the degree of hyponatremia and the presence or absence of symptoms. Another determinant of the regimen that is used is that, although water excretion is impaired, sodium handling is intact since there is no abnormality in volume-regulating mechanisms such as the renin-angiotensin-aldosterone system or atrial natriuretic peptide . It is also important to appreciate the pathogenesis of the hyponatremia in this disorder. The combination of water retention and secondary solute (sodium plus potassium) loss accounts for essentially all of the entire fall in the plasma sodium concentration [2,3]. Their changes occur in the following sequence [3,4]. The hyponatremia is initially mediated by ADH-induced water retention. The ensuing volume expansion activates secondary natriuretic mechanisms, resulting in sodium and water loss and the restoration of near euvolemia. The net effect is that, with chronic SIADH, sodium loss much more prominent than water retention . Severe hyponatremia may also be associated with potassium loss; since potassium is as osmotically active as sodium, the loss of potassium contributes to the reductions in the plasma osmolality and sodium concentration. (See “Treatment of hyponatremia”, section on Effect of potassium). This potassium is derived from the cells and probably represents part of the volume regulatory response . Cells that increase in size due to water entry in hyponatremia lose potassium and other solutes in an attempt to restore cell volume. (See “Symptoms of hyponatremia and hypernatremia”, section on Osmolytes and cerebral adaptation to hyponatremia).
A number of modalities can be used to correct the hyponatremia in the SIADH with water restriction and salt administration being most important [1,5]. The initial rate of correction is primarily determined by the presence or absence of neurologic symptoms attributable to the low plasma sodium concentration. Only patients with symptoms require rapid initial correction; overly rapid correction in any patient should be avoided because it can lead to neurologic complications from osmotic demyelination. (See “Treatment of hyponatremia”, section on Risk of osmotic demyelination). Water restriction Water restriction is the mainstay of therapy in asymptomatic hyponatremia and in chronic SIADH due for example to a small cell carcinoma of the lung. (See “Causes of the SIADH”). The associated negative water balance raises the plasma sodium concentration toward normal. It can also lead to volume depletion due to unmasking of the sodium deficit described above unless sodium intake is also adequate. Subarachnoid hemorrhage Hyponatremia associated with subarachnoid hemorrhage (SAH) may represent a setting in which water restriction is not appropriate. Patients with SAH are at risk for cerebral vasospasm and infarction, the incidence of which is increased by a fall in blood pressure . (See “Treatment of subarachnoid hemorrhage”). This observation has important implications for those patients who become hyponatremic, most often due to SIADH or cerebral salt-wasting. The fall in volume that can occur with fluid restriction for presumed SIADH, which will be more pronounced if the patient actually has cerebral salt-wasting, has been associated with an increased incidence of cerebral infarction . Such patients may best be treated initially with saline, either isotonic or if necessary hypertonic, until it is clear that they are not volume depleted. (See “Causes of the SIADH”, section on Cerebral salt-wasting). Salt administration Severe, symptomatic, or resistant hyponatremia often requires the administration of salt. If the plasma sodium concentration is to be elevated, the osmolality of the fluid given must exceed that of the urine . This can be illustrated by a simple example. Suppose a patient with the SIADH and hyponatremia has a urine osmolality that is relatively fixed at 600 mosmol/kg. If 1000 mL of isotonic saline is given (containing 150 meq each of Na and Cl or 300 mosmol), all of the NaCl will be excreted (because sodium handling is intact) but in only 500 mL of water (300 mosmol in 500 mL of water equals 600 mosmol/kg). The retention of one-half of the administered water will lead to a further reduction in the plasma sodium concentration even though the plasma sodium concentration may initially rise because the isotonic saline is hypertonic to the patient. This hypothetical example has been confirmed in postoperative patients, many of whom have transient SIADH. The administration of isotonic saline or lactated Ringer’s solution to 22 women who had undergone uncomplicated gynecologic surgery resulted in a fall in the plasma sodium concentration in 21 of the patients; the mean fall was 4.2 meq/L . The response is different if hypertonic saline is given. Each liter of 3 percent saline contains 1026 mosmol (513 each of sodium and chloride). Thus, if 1000 mL of this solution is given, all of the NaCl will again be excreted but now in a larger volume of 1700 mL. Thus, after the administration of hypertonic saline, there will be an initial large rise in the plasma sodium concentration and, a smaller effect after the excess sodium has been excreted due to the loss of 700 mL of water. Salt plus a loop diuretic The effect of hypertonic saline (or salt tablets) can be enhanced if given with a drug that lowers the urine osmolality and increases water excretion by impairing the renal responsiveness to ADH. A loop diuretic (such as 20 mg of furosemide once or twice a day) is most often used in this setting, since it directly interferes with the countercurrent concentrating mechanism by decreasing NaCl reabsorption in the medullary aspect of the loop of Henle [1,9]. Demeclocycline or lithium Demeclocycline and lithium act on the collecting tubule cell to diminish its responsiveness to ADH, thereby increased water excretion [1,10,11]. These drugs should be considered only in the rare patient with persistent marked hyponatremia who is unresponsive to or cannot tolerate water restriction, a high salt intake, and a loop diuretic. Demeclocycline (300 to 600 mg twice a day) is more predictably effective and less toxic than lithium . However, renal function should be monitored, since nephrotoxicity can occur . Increased solute intake Dietary manipulation is an alternative method to treat persistent SIADH. In normal subjects, the urine volume is primarily determined by water intake via changes in ADH release. However, when ADH levels are relatively fixed, as in the SIADH, the main determinant of the urine output is the rate of solute excretion which is primarily determined by solute intake. If, for example, the urine osmolality is 600 mosmol/kg in the SIADH, then the urine volume will be 1000 mL/day if solute excretion (sodium and potassium salts and urea) is 600 mosmol/day and 1500 mL/day if solute excretion is increased to 900 mosmol/day with a high salt, high protein diet . Thus, the elevation in the plasma sodium concentration induced by salt occurs in two stages: the direct effect of the ingestion of salt without water, followed by the excretion of the excess salt with water leading to net negative water balance. Unfortunately, many patients with chronic SIADH have a majo r underlying illness (such as an oat cell carcinoma) that limits compliance with increased dietary intake. Urea Another way to use solute excretion to enhance water excretion is the direct administration of 30 g of urea per day [11,12]. This regimen is generally well tolerated, although it should be considered only in patients with marked hyponatremia that does not respond to above modalities. The necessity for chronic therapy is limited to patients with persistent hyponatremia. Many causes of the SIADH are transient, however, resolving as the underlying condition is corrected. Meningitis, pneumonia, and tuberculosis are examples of this phenomenon . (See “Renal disease in tuberculosis”). Vasopressin receptor antagonist Although not currently available for clinical use, ADH receptor antagonists that are selective for the V2 (antidiuretic) receptor are being tested in humans [14-19]. These agents produce a selective water diuresis (without affecting sodium and potassium excretion) that should be beneficial in the SIADH and in hyponatremic patients with congestive heart failure and cirrhosis. In one study, for example, eleven patients with SIADH administered a vasopressin antagonist underwent a water diuresis which was independent of urinary solute excretion . The plasma sodium concentration rose by 3 meq/L over a six-hour period. There is, however, a potential risk of overly rapid correction of the hyponatremia if the ADH effect is completely eliminated. RESET OSMOSTAT Hyponatremia due to a reset osmostat can be seen with any of the causes of the SIADH, and accounts for between 25 and 30 percent of cases overall . Downward resetting of the osmostat can also occur in hypovolemic states (in which the baroreceptor stimulus to ADH release is superimposed on osmoreceptor function), quadriplegia (in which effective volume depletion may result from venous pooling in the legs), psychosis, tuberculosis, and chronic malnutrition [1,20]. The plasma sodium concentration also falls by about 5 meq/L in normal pregnancy; how this occurs is incompletely understood, but human chorionic gonadotropin-induced release of the hormone relaxin may play an important role. (See “Renal function in pregnancy”). The presence of a reset osmostat should be suspected in any patient with apparent SIADH who has mild hyponatremia (usually between 125 and 135 meq/L) that is stable over many days despite variations in sodium and water intake. The diagnosis can be confirmed clinically by observing the response to a water load (10 to 15 mL/kg given orally or intravenously). Normal subjects and those with a reset osmostat should excrete more than 80 percent within 4 hours, while excretion will be impaired in the SIADH . Identification of a reset osmostat is important because the above therapeutic recommendations for the SIADH do not apply in this setting [1,20,21]. These patients have mild, asymptomatic hyponatremia in which there is downward resetting of the threshold for both ADH release and thirst. Since osmoreceptor function is normal around the new baseline, attempting to raise the plasma sodium concentration will increase ADH levels and make the patient very thirsty, a response that is similar to that seen with water restriction in normal subjects. Thus, attempting to raise the plasma sodium concentration is both unnecessary (given the lack of symptoms and lack of risk of more severe hyponatremia) and likely to be ineffective (due to increased thirst). Treatment should be primarily directed at the underlying disease, such as tuberculosis .
Methods used to measure sodium
In patients with a normal or elevated plasma osmolality (called pseudohyponatremia), ion-selective electrodes have been used to directly measure the plasma water sodium concentration. These electrodes, however, have variable accuracy. As an example, many of the electrodes dilute the serum specimen 1:100, which will produce a greater dilution of the plasma water . Suppose that the plasma water (with a normal sodium concentration of 150 meq/L) constitutes 80 percent of the plasma in a patient with hyperlipidemia. In this setting, each liter of plasma contains 120 meq of sodium. If this is now diluted to a total volume of 100 L, there will be only 120 meq of sodium present and, correcting for dilution, the measured sodium concentration will appear reduced at 120 meq/L. Other electrodes directly measure the sodium concentration without dilution. Falsely low levels may still be obtained in patients with hyperlipidemia; why this occurs is not well understood . As an alternative, the water content of plasma in patients with hyperlipidemia or hyperproteinemia can be estimated from the following formula : Plasma water content, percent = 99.1 – (0.1 x L) – (0.07 x P) where L and P refer to the total lipid and protein concentrations in g/L, respectively. When ion-sensitive electrodes were first introduced, the problem of pseudohyponatremia transiently disappeared because the electrode accurately measured the sodium concentration in the liquid phase of serum or plasma (and was then ‘corrected’ to give the concentration that would have been found if the sodium in the liquid phase had been distributed throughout the entire volume, as was the case with flame spectrophotometry). However, someone noted that the performance of the electrode was better at lower-than-physiologic concentrations, so in many labs the sample is diluted in an equal volume of water before measurement. Since the percent of the sample which is liquid phase is smaller in conditions causing pseudohyponatremia, such samples are ‘overdiluted,’ and hence the problem has re-emerged in those labs.
not true hyponatremia
The American Journal of Medicine, Vol 120 (11A), November 2007
Etiologies of dilutional (euvolemic and hypervolemic) hyponatremiaImpaired Renal Free Water Excretion● Euvolemic SIADH X Tumors Pulmonary/mediastinal (bronchogenic carcinoma, mesothelioma, thymoma) Nonchest (duodenal carcinoma, pancreatic carcinoma, ureteral/prostate carcinoma, uterine carcinoma,nasopharyngeal carcinoma, leukemia)X CNS disorders Mass lesions (tumors, brain abscesses, subdural hematoma) Inflammatory diseases (encephalitis, meningitis, systemic lupus, acute intermittent porphyria, multiple sclerosis) Degenerative/demyelinative diseases (Guillain-Barré syndrome; spinal cord lesions) Miscellaneous (subarachnoid hemorrhage, head trauma, acute psychosis, delirium tremens, pituitary stalk section,transphenoidal adenomectomy, hydrocephalus)X Drug induced Stimulated AVP release (nicotine, phenothiazines, tricyclics) Direct renal effects and/or potentiation of AVP antidiuretic effects (DDAVP, oxytocin, prostaglandin synthesisinhibitors) Mixed or uncertain actions (ACE inhibitors, carbamazepine and oxcarbazepine, chlorpropamide, clofibrate; clozapine, cyclophosphamide, 3,4-methylenedioxymethamphetamine [ Ecstasy ], omeprazole; serotonin reuptake inhibitors,vincristine)X Pulmonary diseases Infections (tuberculosis, acute bacterial and viral pneumonia, aspergillosis, empyema) Mechanical/ventilatory (acute respiratory failure, COPD, positive pressure ventilation)X Other AIDS and ARC Prolonged strenuous exercise (marathon, triathalon, ultramarathon, hot-weather hiking) Senile atrophy Idiopathic Glucocorticoid deficiency Hypothyroidism Decreased urinary solute excretionX Beer potomaniaX Very-low-protein diet● Hypervolemic CHF Cirrhosis Nephrotic syndrome Renal failureX AcuteX ChronicExcessive Water Intake● Primary polydipsia● Dilute infant formula● Freshwater drowningACE angiotensin-converting enzyme; AIDS acquired immune deficiency syndrome; ARC AIDS-related complex; AVP arginine vasopressin;CHF congestive heart failure; CNS central nervous system;
>145 mEq/L, >155 is severe
Reduced water intake
- Disorders of thirst perception
- Inability to obtain water
- Depressed mentation
- Intubated patient
Increased water loss
- Vomiting, diarrhea
- Nasogastric suctioning
- Third spacing
- Tubular concentrating defects
- Osmotic diuresis (e.g., hyperglycemia, mannitol)
- Diabetes insipidus
- Relief of urinary obstruction
- Excessive sweating
- Severe burns
Gain of sodium
- Exogenous sodium intake
- Salt tablets
- Sodium bicarbonate
- Hypertonic saline solutions
- Improper formula preparation
- Salt water drowning
- Hypertonic renal dialysate
- Increased sodium reabsorption
- Cushing’s disease
- Exogenous corticosteroids
- Congenital adrenal hyperplasia
can only occur if thirst or access to water is impaired
elderly: often in those with fever or to infirm to get water
infants: diarrhea, they’ll present with hyperpnea, weakness, restlessness, high pitched cry, lethargy, coma
Brain shrinkage from high osmolality can cause cerebral vasculature rupture, this is countered by solute gain in the brain cells if hypernatremia develops slowly. Rapid correction of sodium can lead to cerebral edema.
Stop GI losses, correct pyrexia, hyperglycemia, glycosuria, and withhold lactulose and diuretics. Correct hypercalcemia and hypokalemia.
Maximum correction rate should be 0.5 mmol/L/hour
Aim for 145 as final correction
Oral or Feeding Tube replacement of free water is ideal
If must use IV, use hypotonic fluid (D5W, 0.2% NS, 0.45 % NS) unless severe extracellular dehydraton in which case a short period of NS is usable.
Best Review (NEJM 342:20, p. 1497)
Dosage is highly variable; titrated based on serum and urine sodium and osmolality in addition to fluid balance and urine output I.M., SubQ: 5-10 units 2-4 times/day as needed (dosage range 5-60 units/day) Continuous I.V. infusion: 0.5 milliunit/kg/hour (0.0005 unit/kg/hour); double dosage as needed every 30 minutes to a maximum of 0.01 unit/kg/hour
Safe Sodium Correction
Plasma Na+ replacement Template Is it safe to give?
Max Na+plasma correction per 24 hrs = 8 mmol over 24 hours
Max Na+plasma correction per hour = 2 mmol
Max Na+plasma correction per treatment = 5 mmol over at least 2.5 hrs.
3% NaCl = 513 mmol Na+ per 1000 ml
0.9% NaCl = 154 mmol Na+ per 1000 ml
Plasma Na+correction = [Na+desired] minus [Na+Actual]
= _______ minus _______ = ________ mmol
Can use Na+ 125 or lower as the [Na+desired] for acute correction considering the limits above.
Required Na+ = (Plasma Na+correction) x 0.6 x wt (kg)
Current Patient Weight = ______kg
A: Max 5 mmol Na+correction = 5 x 0.6 x _____ = _____ mmol over 2.5 hrs weight
B: Result A ______ mmol IV x 1000 mL/513 mmol = _________ mL of 3% NaCl
infused over at least 2.5 hrs
C: Compare result A to new MD order:
______ mL of 3% NaCl x 513 mmol/1000 mL = ______ mmol over ____ hrs
Does this exceed the 2.5 hr maximum? ________
Calculate remainder of the maximum allowable plasma Na+correction for the total 24 hr period by using 0.9% NaCl
D: Maximum Na+correction in 24 hr = 8 mmol x 0.6 x ______kg = ________ mmol
E: Already received ______ mL of 3% NaCl x 513 mmol/1000 mL = _______ mmol
F: Result D ____ – Result E _____ = _____ mmol Na+
G: Remaining time balance of 24 minus_____ 3% NaCl infusion time = _____ hrs
H: Result F ______mmol x 1000 mL/154 mmol = ______ mL 0.9% NaClgiven over the remaining time from G______ which is equal to ______ mL/hr
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