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Contraindications for Mannitol in Aphakic Glaucoma
VOL. 91, NO. 2
NOTES, CASES, INSTRUMENTS
265
closure glaucoma. Mannitol can produce potentially dangerous complications, however. In rare instances, these may be fatal. CASE REPORT
Figure (Eartamian and associates). The patient lies prone, elevates the upper body on the arms, and holds the head erect. The ophthalmologist then maneuvers the stretcher and the height of the slit lamp so that the patient's head is in the headrest.
so that the patient's head is in the head rest (Figure). This method is simple and useful for examining bedridden hospital patients sent for ophthalmologic consultation. SUMMARY
Slit-lamp examination of bedridden patients is facilitated by using a stretcher with the patient lying prone and holding the head erect.
CONTRAINDICATIONS FOR MANNITOL IN APHAKIC GLAUCOMA MORRIS T. GRARIE, M.D., ROHERT M. GIPSTEIN, M.D., DONALD A. ADAMS, M.D., AND GERSON W. HEPNER, M.D. Los Angeles, California
Ophthalmologists use mannitol to de crease intraocular pressure in angleFrom the Department of Medicine, Los Angeles New Hospital, Los Angeles, California. Reprint requests to Morris T. Grabie, M.D., 11860 Wilshire Blvd., Los Angeles, CA 90025.
A 72-year-old woman with diabetes mellitus, vas cular hypertension, and mild renal insufficiency was hospitalized after the sudden onset of pain in her right eye. She had undergone cataract surgery on the same eye 13 months previously. Because of diabetic nephropathy and progressive azotemia, an arterial venous fistula had been created in her right forearm to prepare for eventual hemodialysis. Despite her nephropathy, urine output exceeded 1,000 ml/day. Laboratory tests done at the time of admission gave the following values: serum sodium, 128 mEq/liter; serum potassium, 4.7 mEq/liter; serum chloride, 102 mEq/liter; serum carbon dioxide content, 15 mmoles/liter; blood urea nitrogen, 36 mg/100 ml; and serum creatinine, 2.6 mg/100 ml. Visual acuity was no light perception in the right eye and 6/30 (20/100) in the left eye. Intraocular pressure by Goldmann applanation tonometry was R.E. 80 mm Hg and L.E.: 14 mm Hg. The right eyelids were swollen. The conjunctiva was swollen and injected, and there was microcystic edema of the corneal epithelium. The right eye was aphakic and showed rubeosis iridis, an occluded pupil, a small peripheral iridectomy (possibly patent), a shallow anterior chamber caused by secondary pupillary block, and a partial hyphema. The fundus could not be seen by ophthalmoscopy. The left eye was normal, except for a cataract consistent with a visual acuity of 6/30 (20/100). During the ensuing 60 hours, the patient received 1,300 ml of 20% mannitol but there was only a modest decrease in intraocular pressure. Anuria developed and led to severe pulmonary edema with accompanying confusion. Serum sodium concentra tion fell to 99 mEq/liter and serum creatinine rose to 5.2 mg/100 ml (Table). Despite intensive hemodialy sis, /the pulmonary edema, acidemia, and anuria persisted, and the patient died. Serum sodium concentration at the time of death was 112 mEq/liter. DISCUSSION
Mannitol is a six-carbon alcohol deriva tive of mannose and has a molecular weight similar to that of glucose. It disperses uniformly in the extracellular space, is inert, and undergoes little meta bolic change. 1 When renal function is normal, the half-life of mannitol in the circulation is 15 minutes, and 90% of an injected dose is excreted in 24 hours. If renal insufficiency develops, the half-life
266
AMERICAN JOURNAL OF OPHTHALMOLOGY
FEBRUARY, 1981
TABLE CLINICAL FINDINGS AFTER MANNITOL INFUSION
Day Finding
1
2
3
4
Amount of 20% mannitol administered (ml) Serum sodium (mEq/liter) Serum creatinine (mEq/liter) Urine output (ml)
0 128 2.6 1,100
300 114 2.6 700
1,000 102 3.7 0
0 99 5.1 0
of mannitol increases, and the drug is retained in the extracellular space be cause of diminished excretion. Infusion of mannitol creates an increased extracellu lar tonicity and results in transport of water out of cells and into the extracellu lar space. Although mannitol may act as a water diuretic when renal function is normal, and thus induce hypernatremia, 2 its initial osmotic expansion of extra cellular volume lowers the sodium con centration in that compartment. When decreased renal function precludes the removal of free water, the hyponatremia 3 may be profound and lead to lethargy, obtundation, seizures, and coma, as hap pened in this patient. Unlike most other instances of hypona tremia when tonicity also falls, this situa tion may be accompanied by paradoxical hypertonicity. Ordinarily plasma osmo lality is maintained within a rigidly de fined range and perturbations of tonicity in either direction are associated with changes in mentation. In general, the greater the deyiation from a normal os molality, the more pronounced the men tal changes become. Plasma osmolality is increased when mannitol is infused and continues when the substance is retained in the extracellular space. 4 It is this property that leads to the beneficial effect of mannitol in decreasing intracranial pressure and brain edema. 5 Neverthe less, continued infusion in the presence of anuria leads to a rising concentration of
mannitol, and plasma osmolality remains increased despite the decrease in intra cranial pressure and resulting hyponatre mia. Thus, a sustained hyperosmolar state can supervene, as occurred in this case, when the serum osmolality was calculated at 340 mmoles/kg of water. Therefore, both hyponatremia and hyperosmolality may have contributed to the progressive neurologic deterioration. Furthermore, acidosis affecting cerebrospinal fluid p H has been associated with delirium, obtundation, and coma. 6 Silber and Thompson 7 suggested that there is a connection between retained extracellular mannitol and cerebrospinal fluid p H . When dogs with renal insuffi ciency were made acidotic but not given mannitol, cerebrospinal fluid pH re mained normal. When mannitol was ad ministered intravenously to these same animals, cerebrospinal fluid acidosis de veloped and paralleled the level of acidemia. It is possible, therefore, that the persistence of mannitol in this patient may have precipitated cerebrospinal fluid acidosis and contributed in that way to neurologic deterioration. Additionally, mannitol may have con tributed to the progressive renal failure in this patient. Although hypertonic man nitol administered in low concentration generally produces no change in glomerular filtration rate, higher concentrations can induce a decline in both glomerular filtration rate and renal blood flow.8 The
VOL. 91, NO. 2
267
NOTES, CASES, INSTRUMENTS
rapid development of anuria may have been partially related to an adverse effect of high concentrations of mannitol in the blood. Once toxicity is established in the presence of renal insufficiency, extracorporeal hemodialysis is the best therapy. 4 This treatment promotes the rapid re moval of mannitol from the extracellular space, returns plasma osmolality to nor mal, and corrects hyponatremia. Perito neal dialysis has also been used, but in some cases1 this has been associated with a paradoxical increase in plasma osmolali ty and further derangement of neurologic status. SUMMARY
When prescribing mannitol to decrease intraocular pressure, the physician must be alert to potential complications. A 72-year-old woman suffered obtundation, intractable pulmonary edema, acidemia, and irreversible renal insufficiency de spite vigorous hemodialysis. When renal function is compromised, careful monitoring of electrolyte levels, daily urine output, and renal function is necessary with mannitol therapy. REFERENCES 1. Aviram, A., Pfau, A., Czaczkes, J. W., and Ullmann, T. D.: Hyperosmolality with hyponatremia caused by inappropriate administration of mannitol. Am. J. Med. 42:648, 1967. 2. Gipstein, R. M., and Boyle, J. D. : Hypernatremia complicating prolonged mannitol diuresis. N. Eng. J. Med. 272:1116, 1965. 3. Tunner, W. S., Kiser, W. S., and Mann, P.: Studies on the clinical significance of decreased serum sodium levels following the clinical use of mannitol. J. Urol. 94:470, 1965. 4. Borges, H., Hocks, J., and Kjellstrand, C : Severe mannitol intoxication, abstract. Kidney Int. 16:882, 1979. 5. Cottrell, J. E., Robustelli, A., Post, K., and Turndorf, H.: Furosemide and mannitol induced changes in intracranial pressure and serum osmolali ty and electrolytes. Anesthesiology 47:28, 1977. 6. Posner, J. B., and Plum, F.: Spinal fluid pH and neurologic symptoms in acidosis. N. Engl. J. Med. 277:605, 1967.
7. Silber, S. J., and Thompson, N.: Mannitol induced central nervous system toxicity in renal failure. Invest. Urol. 9:310, 1972. 8. Nissenson, A. R., Weston, R. E., and Kleeman, C. R.: Mannitol. West. J. Med. 131:277, 1979.
DIAMOND-COATED ALL-PURPOSE FOREIGN-BODY FORCEPS DYSON HICKINGBOTHAM Durham, North Carolina JEAN-MARIE PAREL, ING.,
ETS-G
Miami, Florida AND ROBERT MACHEMER, M.D. Durham, North Carolina
The removal of intraocular foreign bodies has always been difficult and many instruments have been designed for this purpose. With the advent of intraocular microsurgery, even more sophisticated foreign-body retrievers are needed. Among the desired qualities are precise guidance, minimal distraction during grasping procedures, self-closing mecha nisms to avoid tiring the hand, and better designs for holding the foreign bodies. We have found that existing foreign-body forceps are difficult to manipulate be cause of coarse or counterdirectional movements during grasping maneuvers. A squeeze-handle, for example, necessi tates activation of the instrument, result ing in irregular movements of the tip.
From the Duke University Eye Center, Duke University Medical School, Durham North Carolina (Mr. Hickingbotham and Dr. Machemer), and the Bascom Palmer Eye Institute, University of Miami Medical School, Miami, Florida (Mr. Parel). This study was supported by grant EY02903 from the National Institutes of Health and by a grant from Re search to Prevent Blindness, Inc. (Dr. Machemer). Reprint requests to Robert Machemer, M.D., Duke University Eye Center, P. O. Box 3802, Durham, NC 27710.
NOTES, CASES, INSTRUMENTS
265
closure glaucoma. Mannitol can produce potentially dangerous complications, however. In rare instances, these may be fatal. CASE REPORT
Figure (Eartamian and associates). The patient lies prone, elevates the upper body on the arms, and holds the head erect. The ophthalmologist then maneuvers the stretcher and the height of the slit lamp so that the patient's head is in the headrest.
so that the patient's head is in the head rest (Figure). This method is simple and useful for examining bedridden hospital patients sent for ophthalmologic consultation. SUMMARY
Slit-lamp examination of bedridden patients is facilitated by using a stretcher with the patient lying prone and holding the head erect.
CONTRAINDICATIONS FOR MANNITOL IN APHAKIC GLAUCOMA MORRIS T. GRARIE, M.D., ROHERT M. GIPSTEIN, M.D., DONALD A. ADAMS, M.D., AND GERSON W. HEPNER, M.D. Los Angeles, California
Ophthalmologists use mannitol to de crease intraocular pressure in angleFrom the Department of Medicine, Los Angeles New Hospital, Los Angeles, California. Reprint requests to Morris T. Grabie, M.D., 11860 Wilshire Blvd., Los Angeles, CA 90025.
A 72-year-old woman with diabetes mellitus, vas cular hypertension, and mild renal insufficiency was hospitalized after the sudden onset of pain in her right eye. She had undergone cataract surgery on the same eye 13 months previously. Because of diabetic nephropathy and progressive azotemia, an arterial venous fistula had been created in her right forearm to prepare for eventual hemodialysis. Despite her nephropathy, urine output exceeded 1,000 ml/day. Laboratory tests done at the time of admission gave the following values: serum sodium, 128 mEq/liter; serum potassium, 4.7 mEq/liter; serum chloride, 102 mEq/liter; serum carbon dioxide content, 15 mmoles/liter; blood urea nitrogen, 36 mg/100 ml; and serum creatinine, 2.6 mg/100 ml. Visual acuity was no light perception in the right eye and 6/30 (20/100) in the left eye. Intraocular pressure by Goldmann applanation tonometry was R.E. 80 mm Hg and L.E.: 14 mm Hg. The right eyelids were swollen. The conjunctiva was swollen and injected, and there was microcystic edema of the corneal epithelium. The right eye was aphakic and showed rubeosis iridis, an occluded pupil, a small peripheral iridectomy (possibly patent), a shallow anterior chamber caused by secondary pupillary block, and a partial hyphema. The fundus could not be seen by ophthalmoscopy. The left eye was normal, except for a cataract consistent with a visual acuity of 6/30 (20/100). During the ensuing 60 hours, the patient received 1,300 ml of 20% mannitol but there was only a modest decrease in intraocular pressure. Anuria developed and led to severe pulmonary edema with accompanying confusion. Serum sodium concentra tion fell to 99 mEq/liter and serum creatinine rose to 5.2 mg/100 ml (Table). Despite intensive hemodialy sis, /the pulmonary edema, acidemia, and anuria persisted, and the patient died. Serum sodium concentration at the time of death was 112 mEq/liter. DISCUSSION
Mannitol is a six-carbon alcohol deriva tive of mannose and has a molecular weight similar to that of glucose. It disperses uniformly in the extracellular space, is inert, and undergoes little meta bolic change. 1 When renal function is normal, the half-life of mannitol in the circulation is 15 minutes, and 90% of an injected dose is excreted in 24 hours. If renal insufficiency develops, the half-life
266
AMERICAN JOURNAL OF OPHTHALMOLOGY
FEBRUARY, 1981
TABLE CLINICAL FINDINGS AFTER MANNITOL INFUSION
Day Finding
1
2
3
4
Amount of 20% mannitol administered (ml) Serum sodium (mEq/liter) Serum creatinine (mEq/liter) Urine output (ml)
0 128 2.6 1,100
300 114 2.6 700
1,000 102 3.7 0
0 99 5.1 0
of mannitol increases, and the drug is retained in the extracellular space be cause of diminished excretion. Infusion of mannitol creates an increased extracellu lar tonicity and results in transport of water out of cells and into the extracellu lar space. Although mannitol may act as a water diuretic when renal function is normal, and thus induce hypernatremia, 2 its initial osmotic expansion of extra cellular volume lowers the sodium con centration in that compartment. When decreased renal function precludes the removal of free water, the hyponatremia 3 may be profound and lead to lethargy, obtundation, seizures, and coma, as hap pened in this patient. Unlike most other instances of hypona tremia when tonicity also falls, this situa tion may be accompanied by paradoxical hypertonicity. Ordinarily plasma osmo lality is maintained within a rigidly de fined range and perturbations of tonicity in either direction are associated with changes in mentation. In general, the greater the deyiation from a normal os molality, the more pronounced the men tal changes become. Plasma osmolality is increased when mannitol is infused and continues when the substance is retained in the extracellular space. 4 It is this property that leads to the beneficial effect of mannitol in decreasing intracranial pressure and brain edema. 5 Neverthe less, continued infusion in the presence of anuria leads to a rising concentration of
mannitol, and plasma osmolality remains increased despite the decrease in intra cranial pressure and resulting hyponatre mia. Thus, a sustained hyperosmolar state can supervene, as occurred in this case, when the serum osmolality was calculated at 340 mmoles/kg of water. Therefore, both hyponatremia and hyperosmolality may have contributed to the progressive neurologic deterioration. Furthermore, acidosis affecting cerebrospinal fluid p H has been associated with delirium, obtundation, and coma. 6 Silber and Thompson 7 suggested that there is a connection between retained extracellular mannitol and cerebrospinal fluid p H . When dogs with renal insuffi ciency were made acidotic but not given mannitol, cerebrospinal fluid pH re mained normal. When mannitol was ad ministered intravenously to these same animals, cerebrospinal fluid acidosis de veloped and paralleled the level of acidemia. It is possible, therefore, that the persistence of mannitol in this patient may have precipitated cerebrospinal fluid acidosis and contributed in that way to neurologic deterioration. Additionally, mannitol may have con tributed to the progressive renal failure in this patient. Although hypertonic man nitol administered in low concentration generally produces no change in glomerular filtration rate, higher concentrations can induce a decline in both glomerular filtration rate and renal blood flow.8 The
VOL. 91, NO. 2
267
NOTES, CASES, INSTRUMENTS
rapid development of anuria may have been partially related to an adverse effect of high concentrations of mannitol in the blood. Once toxicity is established in the presence of renal insufficiency, extracorporeal hemodialysis is the best therapy. 4 This treatment promotes the rapid re moval of mannitol from the extracellular space, returns plasma osmolality to nor mal, and corrects hyponatremia. Perito neal dialysis has also been used, but in some cases1 this has been associated with a paradoxical increase in plasma osmolali ty and further derangement of neurologic status. SUMMARY
When prescribing mannitol to decrease intraocular pressure, the physician must be alert to potential complications. A 72-year-old woman suffered obtundation, intractable pulmonary edema, acidemia, and irreversible renal insufficiency de spite vigorous hemodialysis. When renal function is compromised, careful monitoring of electrolyte levels, daily urine output, and renal function is necessary with mannitol therapy. REFERENCES 1. Aviram, A., Pfau, A., Czaczkes, J. W., and Ullmann, T. D.: Hyperosmolality with hyponatremia caused by inappropriate administration of mannitol. Am. J. Med. 42:648, 1967. 2. Gipstein, R. M., and Boyle, J. D. : Hypernatremia complicating prolonged mannitol diuresis. N. Eng. J. Med. 272:1116, 1965. 3. Tunner, W. S., Kiser, W. S., and Mann, P.: Studies on the clinical significance of decreased serum sodium levels following the clinical use of mannitol. J. Urol. 94:470, 1965. 4. Borges, H., Hocks, J., and Kjellstrand, C : Severe mannitol intoxication, abstract. Kidney Int. 16:882, 1979. 5. Cottrell, J. E., Robustelli, A., Post, K., and Turndorf, H.: Furosemide and mannitol induced changes in intracranial pressure and serum osmolali ty and electrolytes. Anesthesiology 47:28, 1977. 6. Posner, J. B., and Plum, F.: Spinal fluid pH and neurologic symptoms in acidosis. N. Engl. J. Med. 277:605, 1967.
7. Silber, S. J., and Thompson, N.: Mannitol induced central nervous system toxicity in renal failure. Invest. Urol. 9:310, 1972. 8. Nissenson, A. R., Weston, R. E., and Kleeman, C. R.: Mannitol. West. J. Med. 131:277, 1979.
DIAMOND-COATED ALL-PURPOSE FOREIGN-BODY FORCEPS DYSON HICKINGBOTHAM Durham, North Carolina JEAN-MARIE PAREL, ING.,
ETS-G
Miami, Florida AND ROBERT MACHEMER, M.D. Durham, North Carolina
The removal of intraocular foreign bodies has always been difficult and many instruments have been designed for this purpose. With the advent of intraocular microsurgery, even more sophisticated foreign-body retrievers are needed. Among the desired qualities are precise guidance, minimal distraction during grasping procedures, self-closing mecha nisms to avoid tiring the hand, and better designs for holding the foreign bodies. We have found that existing foreign-body forceps are difficult to manipulate be cause of coarse or counterdirectional movements during grasping maneuvers. A squeeze-handle, for example, necessi tates activation of the instrument, result ing in irregular movements of the tip.
From the Duke University Eye Center, Duke University Medical School, Durham North Carolina (Mr. Hickingbotham and Dr. Machemer), and the Bascom Palmer Eye Institute, University of Miami Medical School, Miami, Florida (Mr. Parel). This study was supported by grant EY02903 from the National Institutes of Health and by a grant from Re search to Prevent Blindness, Inc. (Dr. Machemer). Reprint requests to Robert Machemer, M.D., Duke University Eye Center, P. O. Box 3802, Durham, NC 27710.