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Severe Mannitol-Induced Hyponatremia Complicating Transurethral Prostatic Resection
0022-534 7/79/1215-0687$02.00/0 Vol. 121, May
THE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
SEVERE MANNITOL-INDUCED HYPONATREMIA COMPLICATING TRANSURETHRAL PROSTATIC RESECTION MICHAEL A. KIRSCHENBAUM From the Division of N ephrology, UCLA School of Medicine, Los Angeles, California
ABSTRACT
A case is presented in which the absorption of mannitol irrigation solution across prostatic veins resulted in severe hyponatremia in a patient undergoing transurethral prostatic resection. Since hyposmolality of the extracellular fluid was not seen because of the presence of mannitol the patient was asymptomatic despite a rapid decrease in the serum sodium concentration to 99 mEq./ 1. The importance of distinguishing dilutional hyponatremia from hyponatremia with normal or elevated osmolality is discussed. More than 30 years ago several investigators postulated that the hypotonic irrigation solutions used during transurethral prostatic resections could enter the prostatic veins and produce hemolysis. 1- 3 The massive hemolysis that occurred resulted in the development of oliguric or anuric renal failure postoperatively in an alarming number of patients. Since that time, water has been replaced as an irrigant by solutions that are nearly isotonic with plasma such as mannitol 4 or glycine 5 and hemolysis has been prevented. The absorption of variable quantities of the irrigating solution by the prostatic veins remains a potential problem and may result in previously unrecognized fluid and electrolyte complications. A case is presented in which the absorption of a substantial amount of mannitol irrigation solution resulted in severe hyponatremia. CASE REPORT
P. P., a 69-year-old white man, was hospitalized for urinary retention. Initial physical examination revealed a healthy appearing, elderly man with a distended bladder and a firm, enlarged prostate. Cystoscopy showed a prostate gland with bilobar lateral hypertrophy. After the patient was stabilized a transurethral prostatic resection was performed. Preoperatively, the serum sodium was 133 mEq./1., potassium 5.0 mEq./1., chlorine 96 mEq./1., total carbon dioxide 22 mEq./1., serum urea nitrogen 90 mg./dl., creatinine 3.5 mg./dl. and glucose 98 mg./dl. The hematocrit was 30 per cent. In the immediate preoperative period the patient received <11. 5 per cent dextrose in water. The operative report revealed considerable bleeding and 30 to 40 1. 3 per cent mannitol solution were needed for bladder irrigation. lntraoperatively, the patient received approximately 1 1. normal saline and 2 units of packed red blood cells. Postoperatively, a continuous bladder irrigation with normal saline was started. Serum electrolytes obtained during the operation revealed the sodium to be 116 mEq./1. and those immediately postoperatively showed that the serum sodium was 99 mEq./1., potassium 4 mEq./1., chlorine 79 mEq./1., total carbon dioxide 11.6 mEq./1., serum urea nitrogen 90 mg./dl. and glucose 200 mg./dl. A serum osmolality was recorded at 290 mOsm./kg. water. Physical examination when the serum sodium was 99 mEq./1. showed the patient to be alert, responsive, appropriate and oriented. Blood pressure was 120/70 mm. Hg and pulse was 84 per minute. The patient was lying comfortably in bed without signs of expansion of the extracellular fluid volume (that is lungs clear to auscultation, neck veins flat and no peripheral edema). The central venous pressure was 4 cm. water. The Accepted for publication August 18, 1978. Supported in part by United States Public Health Service Grant HL 21272 and a grant from the American Heart Association.
patient was assumed to have dilutional hyponatremia and was treated with hypertonic saline solutions and parenteral furosemide. DISCUSSION
Transurethral prostatic resection is a relatively low risk surgical procedure that is associated with few complications. One complication that may arise is severe hyponatremia, which usually is the result of either the inappropriate administration of large volumes of hypotonic intravenous solutions or the absorption of non-sodium containing bladder irrigation solutions. The administration of large volumes of water without sodium lowers the osmolality of the extracellular fluid and causes cellular overhydration. Water entering cells, especially those of the central nervous system, results in the well described syndrome of hyposmolality: confusion, headache, nausea, vomiting, convulsions, coma and death if not treated. 6 Although all forms of hyposmolality of the extracellular fluid are associated with hyponatremia not all cases of hyponatremia are associated with hyposmolality. The presence of high concentrations of a low molecular weight solute in the extracellular fluid may result in marked lowering of the serum sodium without the symptoms of hyposmolality. This patient represents an example of this phenomenon. Overwhelming evidence in this case demonstrates that the patient did not have dilutional hyponatremia in the usual sense for to have lowered the serum sodium from 133 to 99 mEq./1. the patient should have gained approximately 15 1. body water. However, no increase in body water was noted either by physical examination, central venous pressure measurement, hematocrit or, subsequently, body weight. The patient was alert and oriented, suggesting that he was not suffering from an acute decrease in serum osmolality. This suggestion was confirmed by the actual normal measurement of the serum osmolality. To define further the cause of the abnormal serum sodium the serum osmolality, which might be predicted from known osmolality active constituents of the serum, was estimated using the formula 7 serum osmolality (mOsm./kg. water) = 2 sodium + serum urea nitrogen + glucose 3 18
With this formula the serum osmolality was calculated to be 239 mOsm./kg. water. The difference between the measured osmolality and that calculated from the formula was 51 mOsm. The cause of this osmolar gap probably was the absorption of mannitol from the irrigating solution into the vasculature. The mannitol, by transiently increasing extracellular fluid osmolality, obligated a shift of water into the
687
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KIRSCHENBAUM
extracellular fluid space, resulting in profound hyponatremia. The presence of the circulating hexose sugar maintained the osmolality of the serum as the serum sodium decreased, thereby preventing signs and symptoms of hyposmolality. In addition, the marked osmotic diuresis induced by the mannitol prevented the development of volume expansion from the absorption of the irrigating solution. Since 100 mg. per cent of mannitol (MW 182.17) will decrease the serum sodium by 1.6 mEq./1. as much as 300 gm. or 20 per cent of the mannitol used in the irrigation solution may have been absorbed. Hyponatremia is a serious complication of transurethral prostatic resection. It is important to recognize that a decrease in serum sodium may be the result of more than 1 alteration in fluid and electrolyte balance. Dilutional hyponatremia with hyposmolality and hyponatremia with a normal or elevated osmolality must be differentiated from each other before therapy can be instituted. The determination of the measured serum osmolality is an essential test to distinguish these 2 clinical disorders and determining the osmolar gap (that is the difference between the measured and calculated serum osmolality) can be a clue to the presence of other osmotically active solutes. In this patient the hyponatremia was the result of the absorption of mannitol, which maintained the serum osmolality within normal limits and, because of this, no symptoms or signs of hyposmolality were noted despite severe hyponatremia. Aggressive treatment of the hyponatremia with hypertonic saline solutions in an individual with a normal serum
osmolality could result in the development of severe hyperosmolality of the extracellular fluid in an otherwise benign condition. Since mannitol would be excreted the serum sodium eventually would return to normal values. Any impairment in renal function, frequently seen in patients requiring prostatic resection, may modify the excretion rate of mannitol absorbed from irrigation solutions. REFERENCES
1. Creevy, C. D. and Webb, E. A.: A fatal hemolytic reaction following transurethral resection of the prostate gland: a discussion of its prevention and treatment. Surgery, 21: 56, 1947. 2. McLaughlin, W. L., Holyoke, J. B. and Bowler, J. P.: Oliguria following transurethral resection of the prostate gland. J. Urol., 58: 47, 1947. 3. Landsteiner, E. K. and Finch, C. A.: Hemoglobinemia accompanying transurethral resection of the prostate. New Engl. J. Med., 237: 310, 1947. 4. Goodwin, W. E., Cason, J. F. and Scott, W.W.: Hemoglobinemia and lower nephron nephrosis following transurethral prostatic surgery. J. Urol., 65: 1075, 1951. 5. Nesbit, R. M. and Glickman, S. I.: The use of glycine solution as an irrigating medium during transurethral resection. J. Urol., 59: 1212, 1948. 6. Lipsmeyer, E. and Ackerman, G. L.: Irreversible brain damage after water intoxication. J.A.M.A., 196: 286, 1966. 7. Jackson, W. P. U. and Forman, R.: Hyperosmolar nonketotic diabetic coma. Diabetes, 15: 714, 1966.
THE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
Printed in U.S.A.
SEVERE MANNITOL-INDUCED HYPONATREMIA COMPLICATING TRANSURETHRAL PROSTATIC RESECTION MICHAEL A. KIRSCHENBAUM From the Division of N ephrology, UCLA School of Medicine, Los Angeles, California
ABSTRACT
A case is presented in which the absorption of mannitol irrigation solution across prostatic veins resulted in severe hyponatremia in a patient undergoing transurethral prostatic resection. Since hyposmolality of the extracellular fluid was not seen because of the presence of mannitol the patient was asymptomatic despite a rapid decrease in the serum sodium concentration to 99 mEq./ 1. The importance of distinguishing dilutional hyponatremia from hyponatremia with normal or elevated osmolality is discussed. More than 30 years ago several investigators postulated that the hypotonic irrigation solutions used during transurethral prostatic resections could enter the prostatic veins and produce hemolysis. 1- 3 The massive hemolysis that occurred resulted in the development of oliguric or anuric renal failure postoperatively in an alarming number of patients. Since that time, water has been replaced as an irrigant by solutions that are nearly isotonic with plasma such as mannitol 4 or glycine 5 and hemolysis has been prevented. The absorption of variable quantities of the irrigating solution by the prostatic veins remains a potential problem and may result in previously unrecognized fluid and electrolyte complications. A case is presented in which the absorption of a substantial amount of mannitol irrigation solution resulted in severe hyponatremia. CASE REPORT
P. P., a 69-year-old white man, was hospitalized for urinary retention. Initial physical examination revealed a healthy appearing, elderly man with a distended bladder and a firm, enlarged prostate. Cystoscopy showed a prostate gland with bilobar lateral hypertrophy. After the patient was stabilized a transurethral prostatic resection was performed. Preoperatively, the serum sodium was 133 mEq./1., potassium 5.0 mEq./1., chlorine 96 mEq./1., total carbon dioxide 22 mEq./1., serum urea nitrogen 90 mg./dl., creatinine 3.5 mg./dl. and glucose 98 mg./dl. The hematocrit was 30 per cent. In the immediate preoperative period the patient received <11. 5 per cent dextrose in water. The operative report revealed considerable bleeding and 30 to 40 1. 3 per cent mannitol solution were needed for bladder irrigation. lntraoperatively, the patient received approximately 1 1. normal saline and 2 units of packed red blood cells. Postoperatively, a continuous bladder irrigation with normal saline was started. Serum electrolytes obtained during the operation revealed the sodium to be 116 mEq./1. and those immediately postoperatively showed that the serum sodium was 99 mEq./1., potassium 4 mEq./1., chlorine 79 mEq./1., total carbon dioxide 11.6 mEq./1., serum urea nitrogen 90 mg./dl. and glucose 200 mg./dl. A serum osmolality was recorded at 290 mOsm./kg. water. Physical examination when the serum sodium was 99 mEq./1. showed the patient to be alert, responsive, appropriate and oriented. Blood pressure was 120/70 mm. Hg and pulse was 84 per minute. The patient was lying comfortably in bed without signs of expansion of the extracellular fluid volume (that is lungs clear to auscultation, neck veins flat and no peripheral edema). The central venous pressure was 4 cm. water. The Accepted for publication August 18, 1978. Supported in part by United States Public Health Service Grant HL 21272 and a grant from the American Heart Association.
patient was assumed to have dilutional hyponatremia and was treated with hypertonic saline solutions and parenteral furosemide. DISCUSSION
Transurethral prostatic resection is a relatively low risk surgical procedure that is associated with few complications. One complication that may arise is severe hyponatremia, which usually is the result of either the inappropriate administration of large volumes of hypotonic intravenous solutions or the absorption of non-sodium containing bladder irrigation solutions. The administration of large volumes of water without sodium lowers the osmolality of the extracellular fluid and causes cellular overhydration. Water entering cells, especially those of the central nervous system, results in the well described syndrome of hyposmolality: confusion, headache, nausea, vomiting, convulsions, coma and death if not treated. 6 Although all forms of hyposmolality of the extracellular fluid are associated with hyponatremia not all cases of hyponatremia are associated with hyposmolality. The presence of high concentrations of a low molecular weight solute in the extracellular fluid may result in marked lowering of the serum sodium without the symptoms of hyposmolality. This patient represents an example of this phenomenon. Overwhelming evidence in this case demonstrates that the patient did not have dilutional hyponatremia in the usual sense for to have lowered the serum sodium from 133 to 99 mEq./1. the patient should have gained approximately 15 1. body water. However, no increase in body water was noted either by physical examination, central venous pressure measurement, hematocrit or, subsequently, body weight. The patient was alert and oriented, suggesting that he was not suffering from an acute decrease in serum osmolality. This suggestion was confirmed by the actual normal measurement of the serum osmolality. To define further the cause of the abnormal serum sodium the serum osmolality, which might be predicted from known osmolality active constituents of the serum, was estimated using the formula 7 serum osmolality (mOsm./kg. water) = 2 sodium + serum urea nitrogen + glucose 3 18
With this formula the serum osmolality was calculated to be 239 mOsm./kg. water. The difference between the measured osmolality and that calculated from the formula was 51 mOsm. The cause of this osmolar gap probably was the absorption of mannitol from the irrigating solution into the vasculature. The mannitol, by transiently increasing extracellular fluid osmolality, obligated a shift of water into the
687
688
KIRSCHENBAUM
extracellular fluid space, resulting in profound hyponatremia. The presence of the circulating hexose sugar maintained the osmolality of the serum as the serum sodium decreased, thereby preventing signs and symptoms of hyposmolality. In addition, the marked osmotic diuresis induced by the mannitol prevented the development of volume expansion from the absorption of the irrigating solution. Since 100 mg. per cent of mannitol (MW 182.17) will decrease the serum sodium by 1.6 mEq./1. as much as 300 gm. or 20 per cent of the mannitol used in the irrigation solution may have been absorbed. Hyponatremia is a serious complication of transurethral prostatic resection. It is important to recognize that a decrease in serum sodium may be the result of more than 1 alteration in fluid and electrolyte balance. Dilutional hyponatremia with hyposmolality and hyponatremia with a normal or elevated osmolality must be differentiated from each other before therapy can be instituted. The determination of the measured serum osmolality is an essential test to distinguish these 2 clinical disorders and determining the osmolar gap (that is the difference between the measured and calculated serum osmolality) can be a clue to the presence of other osmotically active solutes. In this patient the hyponatremia was the result of the absorption of mannitol, which maintained the serum osmolality within normal limits and, because of this, no symptoms or signs of hyposmolality were noted despite severe hyponatremia. Aggressive treatment of the hyponatremia with hypertonic saline solutions in an individual with a normal serum
osmolality could result in the development of severe hyperosmolality of the extracellular fluid in an otherwise benign condition. Since mannitol would be excreted the serum sodium eventually would return to normal values. Any impairment in renal function, frequently seen in patients requiring prostatic resection, may modify the excretion rate of mannitol absorbed from irrigation solutions. REFERENCES
1. Creevy, C. D. and Webb, E. A.: A fatal hemolytic reaction following transurethral resection of the prostate gland: a discussion of its prevention and treatment. Surgery, 21: 56, 1947. 2. McLaughlin, W. L., Holyoke, J. B. and Bowler, J. P.: Oliguria following transurethral resection of the prostate gland. J. Urol., 58: 47, 1947. 3. Landsteiner, E. K. and Finch, C. A.: Hemoglobinemia accompanying transurethral resection of the prostate. New Engl. J. Med., 237: 310, 1947. 4. Goodwin, W. E., Cason, J. F. and Scott, W.W.: Hemoglobinemia and lower nephron nephrosis following transurethral prostatic surgery. J. Urol., 65: 1075, 1951. 5. Nesbit, R. M. and Glickman, S. I.: The use of glycine solution as an irrigating medium during transurethral resection. J. Urol., 59: 1212, 1948. 6. Lipsmeyer, E. and Ackerman, G. L.: Irreversible brain damage after water intoxication. J.A.M.A., 196: 286, 1966. 7. Jackson, W. P. U. and Forman, R.: Hyperosmolar nonketotic diabetic coma. Diabetes, 15: 714, 1966.