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The syndrome of inappropriate secretion of antidiuretic hormone in the maxillofacial trauma patient
yndrom antidiureti trauma p
inappro hormone
Stuart E. Lieblich, D.M.D.,* David Forman, D.D.S.,** and Bernard D. Gold, D.M.D., * * * * Brooklyn, IV. Y. DIVISION OF ORAL AND MAXiLLOFAClAL HOSPITAL CENTER
Julius Berger, D.D.S.,***
SURGERY, DEPARTMENT OF DENTISTRY, KINGS COUNTY
The maxillofacial trauma patient whose neurologic status undergoes a rapid and serious deterioration may have a severe hyponatremia secondary to the inappropriate secretion of antidiuretic hormone (SIADH). Other causes of hyponatremia must be ruled out, especially posttraumatic cerebral salt wasting, which necessitates a different mode of therapy. A case of SIADH is reported, and the work-up and differential diagnosis of posttraumatic hyponatremia are discussed. (ORAL SURG. ORAL MED. ORAL PATHOL. 59:460-462 1985)
P
atients with maxillofacial injuries often have concomitant head trauma, ranging from a temporary loss of consciousnessto severe increases in intracranial pressure with herniation. Even when no neurologic signs are noted on admission, observation of the patient for any changes in mental status or responsiveness is important to identify any developing cerebral injury. This article reports the case of a multiple-trauma patient who underwent a severeand rapid deterioration in neurologic status as a result of hyponatremia caused by the syndrome of inappropriate secretion of antidiuretic hormone JSIADH). In this syndrome an excess of ADH is secreted, causing the retention of water and a loss of sodium in the urine. Neurologic effects are due to the hyponatremia and are manifested as lethargy, anorexia, apathy, seizures, and, if severe enough, coma. In addition, the expanded plasma volume can cause or increase cerebral edema, exacerbating the original brain injury.’ CASE REPORT
A 14-year-old boy was seen the emergency room of Kings County Hospital after being struck by a car while *Formerly Chief Resident; currently Assistant Professor of Oral and Maxillofacial Surgery; Consultant, United States Veterans Hospital, Newington, Conn. **Formerly Chief Resident; currently in private practice, Levittown and Newtown, Pa. ***Chief, Department of Dentistry. ****Director, Oral and Maxillofacial Surgery. 460
riding a bicycle. Upon admission, his vital signs were stable and he was fully responsiveto stimulus and commands.He reported “blacking out” and had no recollection of the accident. Physical examination revealed a scalp laceration of the left temporal region, a fracture of the left mandibular parasymphysis with intraora1 lacerations, and ecchymosis over the left mastoid (positive Battle’s sign). An abdominal tap and lavage were positive for blood. CT scans of the abdomen and head were carried out prior to surgery. The CT scan of the head was normal, with neither shift nor skull fractures noted. The patient was then taken to the operating room for exploratory laparotomy and a closed reduction of the mandibular fracture. A laceration of the spleen was noted and repaired, and the mandibular fracture was reduced with intermaxillary fixation. Postoperatively, the patient was admitted to the surgical intensive care unit. His postoperative course was unremarkable for 48 hours, when he started to become lethargic and unresponsive, even to family members. Two hours later he had three separate episodes of seizures. A complete blood count and serum chemistry determination showed a sodium level of 121 mEq per liter; potassium, 3.8 mEq per liter; glucose, 89 mg per 100 ml. Blood gasesand hematocrit were within normal limits. Isotonic saline solution was then started at 50 cc per hour. Two hours later the sodium level was 118 mEq per liter. Neurosurgery and medicine consults were ordered and a presumptive diagnosis of SIADH secondary to head trauma was made. Fluids were then restricted to 20 cc of isotonic saline solution per hour. Neurologically, the patient was in a postictal state which gradually improved over the next 24 hours. Urine was collected and the sodium level was noted to be 185
Volume 59 Number 5
mEq per liter with an osmolarity of 452 mOsm per kilogram. Forty-eight hoursafter the onsetof the seizures, the sodliumlevel was I 37 mEq per liter, and there wereno demonstrable neurologic signs. Fluids were slowly increased,and the patient maintaineda smoothpostoperative recovery. DISCUSSION
Antidiuretic hormone is regulated by receptors located in the supraoptic nucleus of the hypothalamus which are sensitive to the plasma osmolarity. The cell bodies in the hypothalamus secrete ADH, which is stored in the posterior pituitary. The response to an increase in serum osmolarity will be stimulation of the posterior pituitary to release ADH into the circulation.2 ADH acts directly at the distal tubules and collecting ducts of the kidney. Here it a.ctivates adenyl cyclase in the epithelial cells, causing an increase in cyclic AMP. The higher levels of cyclic AMP’ cause these cells to become more permeable to water. Water then moves from the luminal side of the nephron into th,e circulation.2 This will cause salt to be lost in the urine, with an increase in the plasma volume. In SIADH, secretion of ADH continues even though the serum osmolarity is low and the plasma volume is expanded. This syndrome was first described in 1957 in two patients with bronchogenic carcinoma.3 Since then, it has been documented in patients with malignant disea.seof the duodenum, pancreas, and thymus, in patients with central nervous system disord.ers,such as meningitis, encephalitis, acute intermittent porphyria, Guillain-Barr& disease, and in head traumas4 Other pulmonary patients, including those with pneumonia and tuberculosis, have been shown to develop SIADH. In order to diagnose SIADH, five criteria. must be met? (1) the patient must have a hyponatremia and hypo-osmolarity of the serum; (2) the urine is not maximally dilute and is of higher osmolarity than the plasma; (3) there ,mustbe a urinary loss of sodium of at least 30 mmol per liter (24-hour urine); (4) normal function of the adrenal, renal, and thyroid glands; and (5) an extracellular fluid volume that is greater than normal. The extracellular fluid volume must be determined to correctly diagnose SIADH and to differentiate it from other causesof hyponatremia. It can be approximated by the following formula’? (1) Current volume body water = 0.6 x Current body weight (kg). (2) Total body solute (mOsm) = Current volume body water (liter) X Plasma osmolarity (mOsm/liter).
Inappropriate
secretion of antidiuretic
hormone
461
(3) ‘Normal volume body water = Total body solute (mOsm) f Desired plasma osmolarity. (4) ICurrent volume body water - Normal volume body water = Body water excess. Thus, in the case presented here the plasma osmolarity was approximated at 250 mOsm per kilogram. By using the above formula, the excess body water was calculated to be 3.1 liters, confirming the diagnosis of SIADH. Hyponatremia will cause neurologic effects which are dependent on the rate of fall in serum sodium as well as its absolute volume. A gradual fall of sodium levels to 120 to 125 mEq per liter will cause lethargy, confusion, anorexia, nausea, and vomiting. Seizures, clonic contractures, and a comatose state can ensue at levels below 120 mEq per liter or sooner if the fall in sodium is drastic, as in this case.’ Other causesof hyponatremia must be ruled out, such as water intoxication. This is usually iatrogenic from fluid overload in the emergency room or during anesthesia. It also occurs in patients with decreased renal function, CHF, or in cases of compulsive polydipsia. Volume excess is present and either pulmonary or peripheral edema may occur. There is an excess of total body water, as well as sodium excess.However, the water overload is more significant and causes a relative hyponatremia. Water restriction is the usual mode of treatment in these cases,with hypertonic saline solution used in severe, symptomatic cases. Another cause of hyponatremia in patients with head trauma involves the concept of cerebral salt wasting. These patients fulfill the laboratory requirements of SIADH (low plasma sodium, low serum osmolarity, urine sodium greater than 25mEq per liter, and a urine osmolarity greater than the serum osmolarity) but have a decreased intravascular volume. Nelson and associates8reported a series of twelve patients with head trauma who developed hyponatremia; and ten of these patients had a decreasedintravascular volume. It is theorized that in these patients there is a defect in the kidney to conservesodium. The causeof the natriuresis is unknown, but there may be an undiscovered natriuretic factor in the brain or an alteration of di.rect neural function to the kidney.9 The urinary sodium loss leads to a decreased intravascular volume rather than the increased intravascular volume, with sodium loss causedby elevation of ADH in SIADH. Fluid restriction in patients with cerebral salt wasting would be deleterious, and their intravascular volume should be corrected with packed red blood cells and isotonic saline solution.8 Hyponatremia may also be associated with excess amounts of another osmotically active substance in
462
LiebEich et al.
the blood. Mannitol, which is often used in the treatment of patients with cerebral injuries, will increase the plasma osmolarity, decreasing the serum sodium. Hyperglycemia will also have the same effect, and a glucose level of 180 mg/dl will lower the sodium levels by 3.5mEq per liter.6 CQNCLIJSIO
SIADH following head trauma is a significant problem. Doczi and associates’ followed a series of 1,808 patients and classified them into groups of mild, moderate, and severehead injuries. They found that 8.2% of the patients with moderate or severe head trauma developed SIADH. The patients with severe head trauma actually had a lower incidence (4.7%) than patients who sustained moderate head trauma (10.6%). They postulated that in patients with severehead trauma fluids were usually restricted from the time of admission, which prevented the manifestations of SIADH. The treatment for patients with SIADH is fluid restriction. Administration of hypertonic saline solution is used only in severecasesand can contribute to vascular overload. In patients who continue a severe downhill course, temporary correction of the sodium level can be achieved by administration of furosemide and replacement of the sodium and potassium lost in the resultant diuresis each hour.‘O Certain drugs, such as demeclocycline,“’ phenytoin, and lithium,‘* have been shown to antagonize ADH. Specific dosage recommendations have not yet been established, but these agents would be useful in patients who cannot tolerate water restriction, as in chronic obstructive pulmonary disease. Before fluids are restricted or certain drugs given, however, other causesof hyponatremia must be ruled out. The most significant of these is cerebral salt wasting which will present similar laboratory data, with the exception of the intravascular volume, and requires a different mode of therapy.
Oral Surg. May, 1985 REFERENCES 1. Doczi T, Tarjanyi .J, Huszka E, Kiss J: Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after head injury. Neurosurgery 10: 685-688, 1982. 2. Cuyton AC: Basic human physiology, Philadelphia, 1977, W.B. Saunders Company, pp, 348, 777. 3. Schwartz WB, Bennett W, Curelop S, Bartter FC: A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 23: 529, 1957. 4. Bartter FC, Schwartz WB: The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42: 790-804, 1967. 5. Isselbacher KJ, et al (editors): Principles of internal medicine, ed. 9, New York, 1980, McGraw-Hill Book Company, p. 1692. 6. Freitag JL, Miller LW (editors): Manual of medical therapeutics, ed. 23, Boston, 1980, Little, Brown & Company, pp. 28-29. I. Coleman JJ: The syndrome of inappropriate secretion of antidiuretic hormone associated with cleft palate: report of a case and review of the literature. Ann Plast Surg 12: 207-212, 1984. 8. Nelson PB, Seif SM: Maroon JC, Robinson AG: Hyponatremia in intracranial disease: perhaps not the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Neurosurg 55: 938-941, 1981. 9. Klahr S, and Rodriquez HJ: Natriuretic hormone. Nephron 15: 387-408, 1975. 10. Hantman D, Rossier B, Zohlman R, Schrier R: Rapid correction of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Ann Intern Med 78: 870, 1973. 11. Forrest JN, Cox M, Hong C, Morrison G, Bia M, Singer I: Superiority of demecloycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 298: 173-177, 1978. 12. Finsterer U, Beyer A, Jensen U, et al: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH)treatment with lithium. Intensive Care Med 8: 223-229. 1982 Reprint requests to: Dr. Stuart Lieblich Department of Oral and Maxillofacial Surgery School of Dental Medicine University of Connecticut Health Center Farmington, CT 06032-9984
inappro hormone
Stuart E. Lieblich, D.M.D.,* David Forman, D.D.S.,** and Bernard D. Gold, D.M.D., * * * * Brooklyn, IV. Y. DIVISION OF ORAL AND MAXiLLOFAClAL HOSPITAL CENTER
Julius Berger, D.D.S.,***
SURGERY, DEPARTMENT OF DENTISTRY, KINGS COUNTY
The maxillofacial trauma patient whose neurologic status undergoes a rapid and serious deterioration may have a severe hyponatremia secondary to the inappropriate secretion of antidiuretic hormone (SIADH). Other causes of hyponatremia must be ruled out, especially posttraumatic cerebral salt wasting, which necessitates a different mode of therapy. A case of SIADH is reported, and the work-up and differential diagnosis of posttraumatic hyponatremia are discussed. (ORAL SURG. ORAL MED. ORAL PATHOL. 59:460-462 1985)
P
atients with maxillofacial injuries often have concomitant head trauma, ranging from a temporary loss of consciousnessto severe increases in intracranial pressure with herniation. Even when no neurologic signs are noted on admission, observation of the patient for any changes in mental status or responsiveness is important to identify any developing cerebral injury. This article reports the case of a multiple-trauma patient who underwent a severeand rapid deterioration in neurologic status as a result of hyponatremia caused by the syndrome of inappropriate secretion of antidiuretic hormone JSIADH). In this syndrome an excess of ADH is secreted, causing the retention of water and a loss of sodium in the urine. Neurologic effects are due to the hyponatremia and are manifested as lethargy, anorexia, apathy, seizures, and, if severe enough, coma. In addition, the expanded plasma volume can cause or increase cerebral edema, exacerbating the original brain injury.’ CASE REPORT
A 14-year-old boy was seen the emergency room of Kings County Hospital after being struck by a car while *Formerly Chief Resident; currently Assistant Professor of Oral and Maxillofacial Surgery; Consultant, United States Veterans Hospital, Newington, Conn. **Formerly Chief Resident; currently in private practice, Levittown and Newtown, Pa. ***Chief, Department of Dentistry. ****Director, Oral and Maxillofacial Surgery. 460
riding a bicycle. Upon admission, his vital signs were stable and he was fully responsiveto stimulus and commands.He reported “blacking out” and had no recollection of the accident. Physical examination revealed a scalp laceration of the left temporal region, a fracture of the left mandibular parasymphysis with intraora1 lacerations, and ecchymosis over the left mastoid (positive Battle’s sign). An abdominal tap and lavage were positive for blood. CT scans of the abdomen and head were carried out prior to surgery. The CT scan of the head was normal, with neither shift nor skull fractures noted. The patient was then taken to the operating room for exploratory laparotomy and a closed reduction of the mandibular fracture. A laceration of the spleen was noted and repaired, and the mandibular fracture was reduced with intermaxillary fixation. Postoperatively, the patient was admitted to the surgical intensive care unit. His postoperative course was unremarkable for 48 hours, when he started to become lethargic and unresponsive, even to family members. Two hours later he had three separate episodes of seizures. A complete blood count and serum chemistry determination showed a sodium level of 121 mEq per liter; potassium, 3.8 mEq per liter; glucose, 89 mg per 100 ml. Blood gasesand hematocrit were within normal limits. Isotonic saline solution was then started at 50 cc per hour. Two hours later the sodium level was 118 mEq per liter. Neurosurgery and medicine consults were ordered and a presumptive diagnosis of SIADH secondary to head trauma was made. Fluids were then restricted to 20 cc of isotonic saline solution per hour. Neurologically, the patient was in a postictal state which gradually improved over the next 24 hours. Urine was collected and the sodium level was noted to be 185
Volume 59 Number 5
mEq per liter with an osmolarity of 452 mOsm per kilogram. Forty-eight hoursafter the onsetof the seizures, the sodliumlevel was I 37 mEq per liter, and there wereno demonstrable neurologic signs. Fluids were slowly increased,and the patient maintaineda smoothpostoperative recovery. DISCUSSION
Antidiuretic hormone is regulated by receptors located in the supraoptic nucleus of the hypothalamus which are sensitive to the plasma osmolarity. The cell bodies in the hypothalamus secrete ADH, which is stored in the posterior pituitary. The response to an increase in serum osmolarity will be stimulation of the posterior pituitary to release ADH into the circulation.2 ADH acts directly at the distal tubules and collecting ducts of the kidney. Here it a.ctivates adenyl cyclase in the epithelial cells, causing an increase in cyclic AMP. The higher levels of cyclic AMP’ cause these cells to become more permeable to water. Water then moves from the luminal side of the nephron into th,e circulation.2 This will cause salt to be lost in the urine, with an increase in the plasma volume. In SIADH, secretion of ADH continues even though the serum osmolarity is low and the plasma volume is expanded. This syndrome was first described in 1957 in two patients with bronchogenic carcinoma.3 Since then, it has been documented in patients with malignant disea.seof the duodenum, pancreas, and thymus, in patients with central nervous system disord.ers,such as meningitis, encephalitis, acute intermittent porphyria, Guillain-Barr& disease, and in head traumas4 Other pulmonary patients, including those with pneumonia and tuberculosis, have been shown to develop SIADH. In order to diagnose SIADH, five criteria. must be met? (1) the patient must have a hyponatremia and hypo-osmolarity of the serum; (2) the urine is not maximally dilute and is of higher osmolarity than the plasma; (3) there ,mustbe a urinary loss of sodium of at least 30 mmol per liter (24-hour urine); (4) normal function of the adrenal, renal, and thyroid glands; and (5) an extracellular fluid volume that is greater than normal. The extracellular fluid volume must be determined to correctly diagnose SIADH and to differentiate it from other causesof hyponatremia. It can be approximated by the following formula’? (1) Current volume body water = 0.6 x Current body weight (kg). (2) Total body solute (mOsm) = Current volume body water (liter) X Plasma osmolarity (mOsm/liter).
Inappropriate
secretion of antidiuretic
hormone
461
(3) ‘Normal volume body water = Total body solute (mOsm) f Desired plasma osmolarity. (4) ICurrent volume body water - Normal volume body water = Body water excess. Thus, in the case presented here the plasma osmolarity was approximated at 250 mOsm per kilogram. By using the above formula, the excess body water was calculated to be 3.1 liters, confirming the diagnosis of SIADH. Hyponatremia will cause neurologic effects which are dependent on the rate of fall in serum sodium as well as its absolute volume. A gradual fall of sodium levels to 120 to 125 mEq per liter will cause lethargy, confusion, anorexia, nausea, and vomiting. Seizures, clonic contractures, and a comatose state can ensue at levels below 120 mEq per liter or sooner if the fall in sodium is drastic, as in this case.’ Other causesof hyponatremia must be ruled out, such as water intoxication. This is usually iatrogenic from fluid overload in the emergency room or during anesthesia. It also occurs in patients with decreased renal function, CHF, or in cases of compulsive polydipsia. Volume excess is present and either pulmonary or peripheral edema may occur. There is an excess of total body water, as well as sodium excess.However, the water overload is more significant and causes a relative hyponatremia. Water restriction is the usual mode of treatment in these cases,with hypertonic saline solution used in severe, symptomatic cases. Another cause of hyponatremia in patients with head trauma involves the concept of cerebral salt wasting. These patients fulfill the laboratory requirements of SIADH (low plasma sodium, low serum osmolarity, urine sodium greater than 25mEq per liter, and a urine osmolarity greater than the serum osmolarity) but have a decreased intravascular volume. Nelson and associates8reported a series of twelve patients with head trauma who developed hyponatremia; and ten of these patients had a decreasedintravascular volume. It is theorized that in these patients there is a defect in the kidney to conservesodium. The causeof the natriuresis is unknown, but there may be an undiscovered natriuretic factor in the brain or an alteration of di.rect neural function to the kidney.9 The urinary sodium loss leads to a decreased intravascular volume rather than the increased intravascular volume, with sodium loss causedby elevation of ADH in SIADH. Fluid restriction in patients with cerebral salt wasting would be deleterious, and their intravascular volume should be corrected with packed red blood cells and isotonic saline solution.8 Hyponatremia may also be associated with excess amounts of another osmotically active substance in
462
LiebEich et al.
the blood. Mannitol, which is often used in the treatment of patients with cerebral injuries, will increase the plasma osmolarity, decreasing the serum sodium. Hyperglycemia will also have the same effect, and a glucose level of 180 mg/dl will lower the sodium levels by 3.5mEq per liter.6 CQNCLIJSIO
SIADH following head trauma is a significant problem. Doczi and associates’ followed a series of 1,808 patients and classified them into groups of mild, moderate, and severehead injuries. They found that 8.2% of the patients with moderate or severe head trauma developed SIADH. The patients with severe head trauma actually had a lower incidence (4.7%) than patients who sustained moderate head trauma (10.6%). They postulated that in patients with severehead trauma fluids were usually restricted from the time of admission, which prevented the manifestations of SIADH. The treatment for patients with SIADH is fluid restriction. Administration of hypertonic saline solution is used only in severecasesand can contribute to vascular overload. In patients who continue a severe downhill course, temporary correction of the sodium level can be achieved by administration of furosemide and replacement of the sodium and potassium lost in the resultant diuresis each hour.‘O Certain drugs, such as demeclocycline,“’ phenytoin, and lithium,‘* have been shown to antagonize ADH. Specific dosage recommendations have not yet been established, but these agents would be useful in patients who cannot tolerate water restriction, as in chronic obstructive pulmonary disease. Before fluids are restricted or certain drugs given, however, other causesof hyponatremia must be ruled out. The most significant of these is cerebral salt wasting which will present similar laboratory data, with the exception of the intravascular volume, and requires a different mode of therapy.
Oral Surg. May, 1985 REFERENCES 1. Doczi T, Tarjanyi .J, Huszka E, Kiss J: Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after head injury. Neurosurgery 10: 685-688, 1982. 2. Cuyton AC: Basic human physiology, Philadelphia, 1977, W.B. Saunders Company, pp, 348, 777. 3. Schwartz WB, Bennett W, Curelop S, Bartter FC: A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 23: 529, 1957. 4. Bartter FC, Schwartz WB: The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42: 790-804, 1967. 5. Isselbacher KJ, et al (editors): Principles of internal medicine, ed. 9, New York, 1980, McGraw-Hill Book Company, p. 1692. 6. Freitag JL, Miller LW (editors): Manual of medical therapeutics, ed. 23, Boston, 1980, Little, Brown & Company, pp. 28-29. I. Coleman JJ: The syndrome of inappropriate secretion of antidiuretic hormone associated with cleft palate: report of a case and review of the literature. Ann Plast Surg 12: 207-212, 1984. 8. Nelson PB, Seif SM: Maroon JC, Robinson AG: Hyponatremia in intracranial disease: perhaps not the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Neurosurg 55: 938-941, 1981. 9. Klahr S, and Rodriquez HJ: Natriuretic hormone. Nephron 15: 387-408, 1975. 10. Hantman D, Rossier B, Zohlman R, Schrier R: Rapid correction of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Ann Intern Med 78: 870, 1973. 11. Forrest JN, Cox M, Hong C, Morrison G, Bia M, Singer I: Superiority of demecloycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 298: 173-177, 1978. 12. Finsterer U, Beyer A, Jensen U, et al: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH)treatment with lithium. Intensive Care Med 8: 223-229. 1982 Reprint requests to: Dr. Stuart Lieblich Department of Oral and Maxillofacial Surgery School of Dental Medicine University of Connecticut Health Center Farmington, CT 06032-9984