Seizures in psychiatric patients

Diagnostics

Seizures in Psychiatric Patients ROBERT SHESSER,

The following case illustrates a serious medical problem that may be encountered in the psychiatric patient. Knowledge of the types of life-threatening metabolic disturbances that may afflict psychiatric patients and familiarity with the proper approach to their diagnosis and treatment is essential for the emergency physician. CASE REPORT A 25-year-old woman who was a resident of a community residence facility was brought to the emergency department in status epilepticus. Community residence facilities are group homes for psychiatric patients who do not need the resources of a hospital, yet who are unequipped and unable to live on their own. The patient had a history of a schizoaffective disorder and had slashed her wrists during several previous suicide attempts. The counselors at the home reported that recently she had been doing well, although she had not been seen by anyone for three hours before she was found in seizure on the floor of her room. There was no evidence in the room of any pills or empty pill containers. She had been taking 300 mg of lithium carbonate and 2 mg of fluphenazine three times per day, both of which were dispensed by counselors at the home. She had no history of any other medical problems. On physical examination, she was seen to be a thin, young female, responsive only to deep pain. She had occasional periods of clonic twitching. Her blood pressure was 112/64 mm Hg, pulse was regular at 122/minute, respiratory rate was 32/minute, and temperature was 36.4”C. There was a large contusion above her right eye. Ear canals and the middle ears were normal. Chest and abdominal examination results were normal. Her optic disks were flat, and she was flaccid and hyporeflexic when not in seizure. Plantar responses were bilaterally upgoing. Her conjunctivae were cheimotic, and there was a doughy quality to the skin, but frank edema was not present.

From the Department of Emergency ington University, 2140 Pennsylvania 20037.

Medicine, George WashAvenue, Washington, DC

Manuscript received September 25, 1984; revision received December 28, 1984; revision accepted January 18, 1985. Address

reprint

Key Words:

requests

Hyponatremia,

to Dr. Shesser. seizures.

MD, MARK SMITH, MD

Inital management included stabilization of the cervical spine and intravenous boluses of 25 g of 50% dextrose and 0.4 mg of naloxone to which there was no response. Results of cervical spinal and skull series were negative for fracture. Serum and urine chemistry analyses results are listed in Table 1. An indwelling bladder catheter was inserted and a urinary output of 2 1 in the first hour was obtained. The patient was treated with intravenous fluids including normal saline solution at 75 mYhr and 5% saline solution over eight hours. She had a total diuresis of 18 1 over the first eight hours of her hospital course. The next morning the patient was alert and awake in the intensive care unit. Serum electrolytes were sodium 130 mEqf1, potassium 3.3 mEq/l, chloride 100 mEq/l, and CO, content 24 mEqf1. Intravenous fluids were then discontinued and the patient resumed normal oral intake of foods, fluids, and medications. No recurrence of the polydipsia was seen, and the patient was discharged on the fourth hospital day.

DISCUSSION This patient manifested a polyuric syndrome with hyponatremia. Polyuria is described as a urinary output greater than two liters per 24 hour period.’ Its differential diagnosis requires a systematic, metabolically grounded approach. Urine has two components-solute particles and water. An excessive urinary output is caused by either a primary increase in solute excretion (termed a solute diuresis) or a primary increase in water excretion. The usual solute particles that cause a solute diuresis are sodium, chloride, glucose, mannitol, urea, bicarbonate, and contrast dye. To decide whether a particular excessive urinary output is caused by either a solute diuresis or a water diuresis, it is helpful to divide the urinary output into two conceptual parts-a solute component that is isotonic to plasma, and a residual free-water component that has no solute particles, which when combined with the solute component results in a urine of observed tonicity. Each component is associated with a theoretical urinary flow called a clearance.2 Osmolar clearance (Cosm) can be defined as the rate (ml/min) that urinary water must be produced to render the solute load that is excreted in the urine isotonic to the plasma. Osmolar clearance is calculated 451

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TABLE 1.

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Laboratory

Serum Sodium Potassium Chloride CO, content Urea nitrogen Creatinine Osmolality Toxicology Lithium Urine* Sodium Potassium Chloride Osmolality

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3, Number

Results

105 mEq/l 3.6 mEq/l 76 mEq/l 19.5 mEq/l 6 mg/dl 0.8 mg/dl 219 mOsm/kg negative for alcohols, anticonvulsants, barbituates 0.6 mEq/l

18 mEq/l 5 mEq/l 20 mEq/l 70 mOsm/kg

*A 30-ml sample was collected bladder catheter.

immediately

after insertion

of a

as: Uosm x Uv/Posm where Uosm = urinary osmolity, Posm = plasma osmolity, and Uv = urinary volume (per minute).2 Free-water clearance (CH,O) is defined as the additional amount of water (ml/min) that must be added to (or subtracted from) the osmolar clearance to result in a urinary flow with the observed osmolality. In cases in which urinary osmolality is greater than serum osmolality, the free-water clearance value will be a negative number. Free-water (CH,O) clearance is calculated as: CH,O = Uv - Uosm.’ In cases of polyuria caused by a solute diuresis, the urinary osmolal excretion is greater than 60 mOsm/hr and the free-water clearance is low, as most of the urniary water is needed to solubilize the increased solute load.3 In cases of polyuria caused by a water diuresis, the free-water clearance is high and the urinary osmolar excretion is low (less than 60 mOsm/hr). In certain cases, a solute diuresis and a water diuresis can coexist in the same patient. Such patients have both a high osmolal excretion (greater than 60 mOsm/hr) and a high free-water clearance (greater than 2 l/24 hours). In this patient’s case, Uv = 2 l/hr = 33 ml/min, Uosm = 70 mOsm/kg H,O, and Posm = 209 mOsm/ kg H,O. Therefore, the Cosm = 10 ml/min. CH,O = 23 ml/min, and the osmolal excretion is 140 mOsm/hr. These values represent an elevation of both the osmolal excretion and the free-water clearance, which suggests that the patient had both a solute diuresis and a free-water diuresis. This combination can be explained by the fact that the patient’s total body volume was probably overloaded. Evidence of volume overload (cheimosis and doughy skin) was present on physical examination. The volume overload led to a reflex decrease in renin and aldosterone secretion, which in turn caused increased urinary sodium excretion de452

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spite the plasma hyponatremia. The most probable sequence of events in this patient was a primary, profound water diuresis (CH,O = 29 l/day) with the high urinary flow rate in the presence of low aldosterone that resulted in a significant obligatory sodium loss and a high osmolal excretion rate (secondary solute diuresis). We can continue the analysis of this patient’s problem by looking at the processes that can cause massive increases in free-water excretion. Only two conditions can do this. Excessive water intake (primary polydipsia) either by iatrogenic administration or from an endogenous thirst disorder can cause such an increase in free-water excretion. Diabetes insipidus, the lack of antidiuretic hormone (vasopressin) activity of either a central (decreased secretion of vasopressin) or nephrogenic (impaired renal tubule responsiveness to vasopressin) etiology, can also cause similar increases in free-water excretion. Problems of water balance occur frequently among patients taking psychotropic medication. Lithium, a common psychotropic medication. is one of the common causes of nephrogenic diabetes insipidus.’ Lithium and halperidol have also been implicated as unusual causes of central diabetes insipidus. When considering diseases of increased water intake, the syndrome of primary polydipsia seems to occur with a much greater frequency in patients with a history of psychiatric disorders than in those without such a history. Much has been written in the medical literature about differentiating diabetes insipidus from excessive water intake.s-9 Normally, a patient presents complaining of either polyuria or polydipsia, and the physician must determine which symptom represents the primary process and which is the result. In diabetes insipidus, the inability to concentrate the urine causes the loss of the large amounts of free water needed to excrete the body’s minimum solute load of at least 600 mOsm/day.‘O As free water is lost, plasma osmolality rises and an osmoreceptor located in the ventromedical and anterior hypothalmus is activated causing the individual to feel thirst. This system is sensitive to as little as a l-2% rise in serum osmolality.” Should the patient be unable to replace his urinary free-water losses with fluid, he would soon achieve a state of hypertonic dehydration. In cases of primary polydipsia, the excessive water intake is quite properly excreted in the urine. Sometimes the water diuresis causes large urinary electrolyte losses that can result in severe metabolic problems. Table 2 compares central and nephrogenic diabetes insipidus with primary polydipsia. Therefore, the best explanation for the primary water diuresis in this patient is massive water ingestion

SHESSER

TABLE 2.

Comparison

of Central

and Nephrogenic

Diabetes

Central Onset Diuresis Sex (male/female) Psychiatric history

Abrupt Continuous l/l None

Serum vasopressin level Serum osmolality (mOsm/l)

Low >275

insipidus

DI

(3-15

AND SMITH n SEIZURES

(DI) with Primary Nephrogenic

l/day)

(primary polydipsia). Diabetes insipidus does not produce the degree of volume expansion that was seen in this patient (which is much more consistent with water overload) nor does it result in either the extraordinarily high urinary flow rates or low serum osmolality that were seen. The next phase in the analysis of this patient’s problem is to understand her serum electrolytes. The most striking electrolyte abnormality in this patient was the profound depression of the serum sodium. When evaluating the hyponatremic patient, the key question the physician should address is whether the patient is volume depleted, volume overloaded, or euvolemic.1*12-16 In this patient’s case, although there was evidence of fluid overload, there were no clinical data suggesting the presence of nephrosis, cirrhosis, or congestive failure, which are the most common causes of hyponatremia with edema. The patient had a urinary sodium level of 18 mEq/l; all of these other common causes of fluid-overload states are frequently accompanied by very low (less than 5 mEq/l) urinary sodium excretions.’ The possibility that the hyponatremia was caused by an inappropriate vasopressin secretion (Le., syndrome of inappropriate antidiuretic hormone [SIADH]) can be eliminated because polyuria is not seen in patients with elevated vasopressin. Furthermore, the patient’s urine was maximally dilute (Uosm = 70 mOsm/kg) compared with the serum (Posm = 214 mOsm/kg) and in the presence of vasopressin, the urine is concentrated. Maximal urinary dilution indicates an absence of vasopressin secretion; absence of vasopressin secretion is the appropriate response to ingestion of a massive amount of water.‘O The proper conclusion is that the patient had a primary water diuresis (not solute diuresis), that the water diuresis was caused by massive water ingestion (not diabetes insipidus), and that the massive water ingestion caused a sodium diuresis. This combination of events leads to an acute decrease in the serum sodium that in turn caused seizures and encephalopathy. The volume of the patient’s water ingestion had to be immense to cause her hyponatremia. Humans are able to drink 18 to 24 1 of water per day (20 ml/min) without any change in serum tonicity. This patient had a free-

IN PSYCHIATRIC

PATIENTS

Polydipsia DI

Variable Continuous (3-5 l/day) 111 Yes, only in cases of lithium intoxication High >275

Primary Vague intermittent 4/l Yes

Polydipsia

(3-30

l/day)

Low ~275

water clearance of 23 mllmin, implying that she was drinking water at a rate of greater than 29 I per 24 hours before presentation. Compulsive water drinking (psychogenic polydipsia) is a syndrome that is seen in patients with a broad spectrum of underlying psychopathology. 17,18 Blum ef ~1’~have identified some degree of polydipsia in 17.5% of patients in a general psychiatric ward. Schizophrenia, alcoholism, and personality disorders were the most frequent diagnoses associated with polydipsia, although polydipsia has been seen in patients with a wide range of psychiatric problems. In ambulatory patients, increasing drinking is often seen as a response to exogenous stressZO In general, the polydipsia accompanies an exacerbation of the patient’s psychiatric disorder, and it is often controlled after adjustments in patient’s psychotropic medications bring the psychiatric disorder under better control. Since this syndrome of compulsive water drinking was first described in 1923,*Oit has been observed that some patients remain relatively well and are able to maintain sodium tonicity in the low normal range, while others develop marked encephalopathy secondary to profound hyponatremia. Three explanations have been suggested. Inappropriate ADH secretion. Several authors2’-Z3 have indicated both direct (elevated vasopressin levels) and indirect (inappropriate high urinary osmolality compared with serum osmolality) evidence for inappropriate antidiuretic hormone (ADH) secretion in groups of polydipsic patients presenting with profound hyponatremia. Raskind et aP3 postulate that a primary limbic-system disturbance may be responsible for the thought disorder, the polydipsia, and the inappropriate antidiuretic hormone secretion. Though it is clear that SIADH is operative in some of these patients, it is not universally present in hyponatremic polydipsics. Reset omostat. Haniprasad et a124 indicated that though the patients studied secreted an appropriately dilute urine when their plasma osmolality was very low, their urine became prematurely hypertonic when their plasma osmolality increased to only 242-272 mOsm/kg (normal 290 mOsm/kg). Antipsychotic treatment tended to normalize this phenomenon. The au453

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thors concluded that a resetting of osmotic regulation occurred in patients who consumed large amounts of water over long periods of time and that this lead to a chronic depression of their plasma osmolality (chronic hyponatremia). Pure-water irztoxication. Despite a person’s ability to excrete massive quantities of free water, it is still possible in the short run to ingest more water than can be excreted.?’ Such behavior leads to overhydration and acute dilutional hyponatremia. The metabolic encephalopathy that ensues from the hyponatremia terminates the water drinking. The patient in question seems to have fallen into the category of pure-water intoxication. Her urine was maximally dilute, suggesting an absence of vasopressin effect. With treatment, her serum osmolality returned to and remained normal, suggesting that her osmostat was normal. The urgency of treatment of the hyponatremic patient is dictated by the state of the patient’s sensorium. As a person becomes hyponatremic, the first symptoms will be nausea, emesis, and abdominal and muscular cramps. These will be followed by lethargy. confusion, delirium. seizures, and coma. Though there is no absolute correlation between central nervous system (CNS) symptoms and level of serum sodium. Arieff and GuisadaoZh suggest that the length of time during which the hyponatremia developed may play an important role. Patients with acutely developing hyponatremia have more CNS symptoms at equivalent serum sodium levels than those patients in whom the hyponatremia developed gradually. The pathophysiology of changes in mental status in acute hyponatremia is thought to be cerebral edema. Water moves out of the extracellular space into cells in order to maintain osmolar equilibrium. Cerebral edema has been confirmed by autopsy studies in patie’nts who died after an acute water overload. In chronic hyponatremia, the cause for the neurological disturbance is different. In these patients there will be time for a compensatory loss of intracellular electrolytes that will minimize the movement of water toward the intracellular space, and there is an absence of cerebral edema. This intracellular electrolyte depletion does, however. lead to diffuse cellular dysfunction secondary to both an inhibition of brain-energy metabolism and interference in neurotransmitter release.Z6 In hyponatremic patients who are suffering from water intoxication but have minimal CNS impairment, water restriction will be sufficient treatment if they are excreting a maximally dilute urine (less than 80 mOsm/ kg). In the water-overloaded patient, 8% of the fluid load remains intravascular. If enough water is ingested, the intravascular portion of the fluid load will be sensed by systemic volume receptors. This in turn 454

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leads to a decrease of renin and aldosterone secretion and causes an increased amount of sodium (greater than 20 mEq/l of urinary sodium) to be excreted in the urine along with water. Such increased sodium excretion accounts for the dual disorder of both a water diuresis and solute diuresis found during the initial analysis of such patients. These patients may then become total-body sodium-depleted, in addition to being water-overloaded. Such may have been the case with our patient. Patients who are comatose or are having seizures from hyponatremia have been reported to have a mortality rate as high as 50%.‘” Therefore, an aggressive treatment approach that includes the administration of hypertonic (5% = 860 mmolil) saline solution has been recommended. Unfortunately. there are no data to show that a rapid correction of hyponatremia results in a better neurological prognosis than water restriction alone. Nonetheless, the literature is unanimous in stating that hypertonic saline solution should be given to hyponatremic patients with profound changes in mental status.‘.Z6-Zx It is not known with certainty the maximal rate at which serum sodium level can be raised without precipitating CNS hemorrhage, the main complication reported with rapid salt loading in both man and animals. The physician must. therefore, take care to avoid too rapid a correction of hyponatremia. When using hypertonic saline, the amount of exogenous sodium needed to normalize a patient’s serum sodium must first be calculated as follows: Total serum replacement (mEq) = (140 mEq/l - patient’s serum sodium) x (wt in kg) x (0.5) Half of the calculated deficit should be administered over the first eight hours and treatment should be continued until the patient achieves a serum sodium level of 130 mEq/l or until neurological findings resolve.” An infusion of 5% saline solution at 70 mEq/h has been shown to raise serum sodium by an average of 2-3 mEq/l/hr.26 Ongoing sodium losses from a solute diuresis can be replaced by concomitant normal saline replacement on a milliequivalent per milliequivalent basis. The amount of hypertonic saline and normal saline that this patient needed can be calculated as follows: serum sodium, 105 mEq/l, patient weight, 100 kg, urinary sodium 18 mEq/l, and urinary output 2 l/hour). Hypertonic Saline (to raise serum sodium) (140-105) x 100 x (0.5) = 1750 mEq total sodium deficit -875 mEq to be administered in the first 8 hours -1 1 of 5% saline = 860 mEq -Therefore. administer 5% saline solution at 125

SHESSER

ml/hr for 8 hours (should raise serum sodium 3 -5 mEq/l/hr) Normal Saline (to replace ongoing serum sodium losses) urine loss = 36 mEq/hr -therefore, administer normal saline solution at 200 ml/hr In this patient the polyuria was the appropriate response to acute overhydration from water ingestion. If left alone, she would have certainly regulated her serum tonicity on her own, but would have eventually become sodium-depleted from the solute diuresis. Hypertonic saline solution administration was indicated because of her seizures and her profound changes in mental status. CONCLUSION This patient presented with polyuria and hyponatremia secondary to psychogenic polydipsia. The availability of the modern laboratory makes the diagnosis quite straightforward, as other causes of hyponatremia and polyuria can be easily and systematically eliminated by evaluating serum and urinary electrolytes and osmolality. The emergency physician should be aware of the diagnostic and therapeutic considerations in the severely hyponatremic patient and should be able to rapidly initiate the proper treatment. Once the metabolic situation is stabilized, the patient should receive intensive inpatient psychiatric reevaluation to correct the exacerbation of the underlying psychiatric condition that led to the polydipsia. REFERENCES 1.Taclob 2. 3. 4. 5.

6. 7.

LT, Needle MA. Hyponatremic syndromes. Med Clin North Am 1973;57:1425-1432. Bed T, Anderson RJ, McDonald KM, et al. Clinical disorders of water metabolism. Kidney Int 1976;10:117-132. Kleeman CR, Fichman MP. The clinical physiology of water metabolism. N Engl J Med 1976;227:1300-1306. Lydiard RB, Gelenberg AJ. Hazards and adverse effects of lithium. Ann Rev Med 1982;33:327-344. Dies F, Rangel S, Rivera A. Differential diagnosis between diabetes insipidus and compulsive polydipsia. Ann Intern Med 1981;54:710-725. McDonald KM, Miler PB, Anderson RL, et al. Hormonal control of water excretion. Kidney Int 1976;10:38-45. Moses AM, Miller M. Drug-induced dilutional hyponatremia. N Engl J Med 1974;291:1234-1237.

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PATIENTS

8. Moses AM, Streeten MB. Differentiation of polyuric osmolality induced by hypertonic saline infusions. Am J Med 1976;42:368-377, 9. Saruta T, Fujimaki M, Ogihara T, et al. Evaluation of reninangiotensin system in diabetes insipidus and psychogenic polydipsia. Nephron 1982;32:14-17. 10. Robertson GL, Shelton RL, Athar S. The osmoregulation of vasopressin. Kidney Int 1976;10:25-37. 11. Anderson 6, Rungren DVM, Rungren M. Thirst and its disorders. Ann Rev Med 1980;33:231-239. 12. Asraf N, Locksley R, Arieff Al. Thiazide induced hyponatremia associated with death or neurologic damage in outpatients. Am J Med 1981 ;10:117-132. 13. Defronzo RA, Goldberg M, Zalman SA. Normal diluting capacity in hyponatremic patients. Ann Intern Med 1976;84:538-554. 14. Fichman MP, Vorherr H, Kleeman CR, et al. Diuretic-induced hyponatremia. Ann Intern Med 1971;75:853-863. 15. Friedler RM, Koffle A, Kurokawa K. Hyponatremia and hypernatremia. Clin Nephrol 1977;7:163-172. 16. Kennedy RM, Earley LE. Profound hyponatremia resulting from a thiazide-induced decrease in urinary diluting capacity in a patient with primary polydipsia. N Engl J Med 1970;282:1185-1187. 17. Mandell AJ, Mersol-Sabbot I, Mandell MP. Physiological disturbance and water retention. Arch Gen Psychiatry 1964;10:513-518. 18. Mendelson WB, Deza DC. Polydipsia, hyponatremia, and seizures in psychotic patients. J Nerv Ment Dis 1976;162:140-143. 19. Blum A, Tempey FW, Lynch WJ. Somatic findings in patients with psychogenic polydipsia. Clin Psychiatry 1973;44: 2-10. 20. Barlow ED, De Wardner HE. Compulsive water drinking. Cl J Med 1959;28:110-125. 21. Dubovsky SL, Grabob S, Berl T, et al. Syndrome of inappropriate secretion of antidiuretic hormone with exacerbate psychosis. Ann Intern Med 1973;79:551-554. 22. Hobson JA, English M. Self-induced water intoxication. Ann Intern Med 1963;58:324-332. 23. Raskind MA, Orenstien H, Cristopher TG. Acute psychosis, increased water ingestion, and inappropriate antidiuretic hormone secretion. Am J Psychiatry 1975;132:907-910. 24. Hariprasad MK, Eisinger RP, Nadler IM, et al. Hyponatremia in psychogenic polydipsia. Arch Intern Med 1982;140: 1639-1642. 25. Langgard H, Smith WO. Self-induced water intoxication without a predisposing illness: A report of two cases. N Engl J Med 1962;666:378-381. 26. Arieff AT, Guisadao R. Effects on the central nervous system of hypernatremic states. Kidney Int 1976;10:104-116. 27. Arieff Al, Llach F, Massry SG. Neurological manifestations and morbidity of hyponatremia: Correlation with brain water and electrolytes. Medicine 1976;55:121-128, 28. Goldberg M. Hyponatremia. Med Clin North Am 1981;65: 2.51-269.

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