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Ocular Osmotherapy with Mannitol
OCULAR OSMOTHERAPY WITH KEVIN
HILL,
MANNITOL
M.D.
Waterville, Maine CHjOH I HOCH I HOCH
The use o f osmotic agents to lower intraocular pressure dates back to the investigations o f Cantonnet^'^ and Hertel.' Several osmotically active substances*'^ have been tried through the years but they have not been entirely satisfactory. Recently, intravenous hypertonic urea has been used extensively but it, too, is not without disadvantages.
HCOH
I
intervals thereafter. T h e same Schiøtz tonometer was used and the readings were converted on the basis o f the 1955 scale. All patients were observed and questioned f o r sideeffects and, in most instances, a special note was made o f the approximate depth o f the anterior chamber.
RESULTS
T h e patients to w h o m mannitol infusions were given can be divided into four groups, based upon the particular clinical problem which each patient presented: 1. Angle-closure glaucoma. Five patients presented with high ocular tension due to acute closure of the anterior chamber angle. T h e diagnosis was confirmed b y gonioscopy in all cases. It is interesting that three o f the patients developed acute angle closure while receiving miotics. A fourth case was treated initially with pilocarpine, eserine and acetazolamide without a satisfactory lowering o f ocular tension.
Mannitol solution f o r intravenous use is readily available and does not require mixing prior to administration. Prewarming the solution to prevent crystallization at room temperature has been recommended but this has not been routinely necessary in the present study. MATERIALS
T h e dosage o f mannitol administered to these patients varied (table 1) but in all instances there was a prompt fall in ocular tension which was maintained by miotics or carbonic anhydrase inhibitors until glaucoma surgery could be performed (fig. 2 ) . T h e depth and gonioscopic appearance o f the anterior chamber was observed in four cases after the ocular tension had been lowered
All patients in the study received an intravenous infusion o f 20-percent mannitol solution.* Fluids were denied the patients during the infusion period. The ocular tension was determined immediately before the infusion was started and at various short * Kindly supplied by Martin McGaw Laboratories, Inc.
Roberts,
Milliosmoles/100 gm. = S49
CHjOH Fig. 1 (Hill). The structure of mannitol.
Mannitol is a 6-carbon hexahydric alcohol (fig. 1 ) which is stable in solution. A d ministered intravenously, it is distributed throughout the extracellular fluid compartment and is not significantly metabolized by the body. It is rapidly and totally excreted b y filtration through the renal glomeruli and is not reabsorbed by the tubules.
A N D
Distribution; Extracellular fluid compartment.
HCOH
Because o f the continuing search f o r an effective ocular hypotensive agent without side-effects, a clinical investigation of mannitol has been undertaken during the past 18 months. T h e usefulness o f mannitol in other fields of medicine has been well documented'"^" and a few reports o f the ophthalmic uses of this agent have already appeared.^^"^'
METHOD
Molecular VVeight = 182.17
Ph.D., 79
80
KEVIN
HILL
TABLE 1 DOSAGE OF 20 PERCENT MANNITOL AND ASSOCIATED SIDE-EFFECTS Mannitol Dosage tictac
Side-Effects
i>υ.
gm./kg.
gm./kg./hr.
ml./min.
1.00 1.80 3.10 1.67 0.66
1..« 1.00 2.00 3.34 2.64
9.0 5.0 10.5 16.7 16.7
None None Chilly sensation None None
1.03 1.85
1.03 2.47
5.0 11.1
None Mild headache
0.75 0.70 1.60 1.60 1.76 0.90 1.20
1.12 1.40 3.20 3.20 2.63 1.35 1.60
7.5 10.0 13.3 13.3 16.7 9.0 10.0
None None None None None None None
1.40
0.93
6.25
.None
Angle-closure Glaucoma 1 2 3 i 5 Secondary Glaucoma 6 7 Dangerous Eyes 8 9 10 11 12 13 14 Hyphema IS
CASE NUMBER
Fig. 2 (Hill). The effect of 20-percent mannitol on the ocular tension in acute angle-closure glau-
* The numbers at the top of the columns in Figures 2, 3, 4 and 5 indicate the percentage fall in ocular tension.
by mannitol and n o change from the preinfiision examination was noted. 2. Secondary glaucoma. T w o patients with open-angle glaucoma and anterior uveitis pre sented with elevated ocular tension which was not satisfactorily lowered b y intensive topical anti-inflammatory therapy (atropine and corticosteroids) and carbonic anhydrase inhibitors. It is possible that the local steroids may have contributed to the intractability o f the glaucoma in these cases but this was not definitely proved. Mannitol infusions (table 1) promptly lowered the ocular tension in both patients (fig. 3 ) despite the presence of a partially "broken-down" blood-aqueous barrier, as evidenced b y the presence o f cells and flare in the anterior chamber in Case 6 and a flare without cells in the anterior cham ber in Case 7. 3. "Dangerous eyes" undergoing cataract surgery. These patients were mostly younger middle-aged adults with dense pos terior subcapsular cataracts with the possi bility o f a firm adhesion o f the posterior cap sule to the hyaloid. Some of them also had
81
OCULAR OSMOTHERAPY W I T H MANNITOL
UREA O.agm./kg.
•
UREA 1.3gin./ttg.
I n i t i a l ocular tension
I
Ocular t e n s i o n at end o f mannitol Infualon
Ocular TeneIon
MANNITOL 1.4gni,/kq.
CASE NUMBER
Fig. 3 (Hill). The effect of 20-percetit mannitol on the ocular tension in secondary glaucoma.
the heavy-set, bull-necked physique, promi nent eyes and tight lids which are associated with the increased likelihood of vitreous loss. A mannitol infusion was started 30 to 45 minutes before cataract surgery (table 1 ) . In all instances, the ocular tension fell to low levels (fig. 4 ) and cataract extraction was uneventful. 4. Hyphema and secondary glaucoma. Following cataract extraction, a patient de veloped iris prolapse which required repair of the wound. Subsequently, a nearly total hyphema with secondary glaucoma de veloped. The tension was not satisfactorily lowered by large oral doses o f acetazolamide and early hemosiderosis o f the cornea was noted. Because of the apparent beneficial ef fects of intravenous hypertonic urea upon hyphema reported by Kwitko,'^ an infusion of 30-percent urea solution was adminis tered. T h e ocular tension promptly fell but no significant change in the blood clot within the anterior chamber was noted. A repeat
I n i t i a l ocular
Fig. 5 (Hill). The effect of 30-percent urea and 20-percent mannitol on ocular tension in hyphema (Case 1.Í).
infusion o f urea on the following day also lowered the ocular tension but was without obvious eifect upon the hyphema. Four days later, with little change in the hyphema and with recurrence o f increased ocular tension, an infusion o f 20-percent mannitol was given. Again, there was a prompt fall in ocular tension but n o visible effect upon the clot.. Subsequently, the clot was removed surgically with the aid o f fibrinolysin. T h e ocular hypotensive effects o f urea and mannitol in this patient are sum marized in Figure 5. O f interest is the fact that during both urea infusions administered through differ ent antecubital veins, a moderate burning sensation at, and proximal to, the needle site was noted by the patient. T h e infusion needles were tested and thought to be well positioned in the vein. A f t e r the first urea infusion, a mild phlebitis developed. The subsequent administration of maimitol was without any noticeable effect upon the vein.
• Fig. 4 (Hill). The effect of 20percent mannitol on the ocular ten sion in nonglaucomatous patients undergoing cataract surgery.
mm. Hg. schletz
O c u l a r t e n s i o n a t end mannitol infusion
of
KEVIN HILL
82
minutes, and the duration o f effect is approx
SIDE-EFFECTS
A s summarized in Table 1, the side-effects associated with the intravenous administra tion of mannitol were mild and few. Head ache and chilis appear to be the most fre quently occurring side-effects reported thus far. It should be noted that in some patients with acute angle-closure glaucoma, headache is relieved by the reduction o f ocular tension during
mannitol
infusion.
Other
reported
side-effects o f mannitol, such as dizziness, rhinitis, urinary retention, nausea, phlebitis and chest pain,""^^ were not noted in the present series. Accidental extravasation o f mannitol has occurred at the
infusion
site and,
unlike
urea, has not produced severe tissue necrosis. Although irritation of veins by 20-percent mannitol has been reported, the comparative obser\'ations already noted suggest that man nitol is less irritating than urea in this re spect. Other disturbing side-effects, such as severe back pain and disorientation
which
have been described f o r urea,^' have not, as yet, been observed following mannitol
ad
ministration.
imately five to seven hours depending upon the state of the blood-aqueous barrier and the fluid intake o f the patient. F o r most patients in w h o m the achievement o f ocular hypoten sion is desirable, a dosage o f I.O or 2.0 g m . / kg. administered in 30 to 60 minutes appears to be satisfactory. F o r those cases, such as the patients undergoing cataract surgery in whom the initial ocular tension is not high, a lower total dose will be necessary to achieve a satisfactory hypotensive effect. A reason able rate f o r the infusion o f the 20-percent mannitol solution is 10 ml./min.,
although
considerably more rapid rates o f administra tion have been well tolerated (table 1 ) . Personal experience in the use o f both agents bears out the impression o f other in vestigators that mannitol has certain advan tages over urea. Mannitol does not elevate the blood urea nitrogen content and thus is preferable in patients with poor renal func tion.'' It is not significantly metabolized b y the body and can be used safely in patients who must restrict their consumption o f car bohydrates. The side-effects observed thus far appear to be less troublesome than those
CO.MMENT
of urea. F o r example, mannitol appears to
In this series of cases, a 20-percent solu tion o f mannitol proved to be an effective ocular hypotensive agent. Like urea, manni tol lowers ocular tension by virtue o f its o s motic effect. Blood osmolality studies"' indicate the close correlation between changes in blood osmolality and ocular ten sion. Careful gonioscopy in cases of acute angle-closure glaucoma indicates that the hy potensive effect of mannitol is not dependent upon reopening o f the usual channels for aqueous outflow, f o r the ocular tension is lowered despite obvious continued closure of the anterior chamber angle. In some in stances, deepening o f the anter'or chamber after mannitol infusion has been reported'^ but careful observation o f the present series of patients could not confirm this.
be less injurious than urea when it is extrav-
The hypotensive action o f mannitol is prompt, a definite effect appearing within 30
sibility of untoward effects should be con
asated. Mannitol solution is also more stable and does not require the bothersome prepara tion necessary with urea. This is not to say that hypertonic manni tol solution is entirely innocuous. T h e rapid administration of large doses of mannitol to patients with cardiac failure or low cardiac reserve, especially if renal function is im paired, may be hazardous due to rapid e x pansion o f the extracellular fluid space and consequent overloading o f the cardiovascular system.
Electrolyte
imbalance
may
result
from the sodium diuresis caused by mannitol infusion."'-" mannitol
Repeated
administration
( o r any osmotic agent)
of
without
adequate fluid replacement could lead to a marked state of hyperosmolarity. T h e pos sidered and all patients receiving intravenous
OCULAR OSMOTHERAPY W I T H MANNITOL
83
mannitol should be carefully evaluated before
sodes o f glaucoma (angle-closure, malignant,
and
and secondary types) and in the preoperative
observed during administration o f this
agent.
preparation o f
certain patients
cataract extraction in w^hom the
S U M M A R Y
. c cc roo T h i s study confirms the emcacy o f ZO-per-
undergoing danger o f
vitreous loss appears likely. ^^^^ ^ Avenue
cent mannitol as an ocular hypotensive agent in a variety o f clinical ophthalmic conditions. Mannitol side-effects
is
easily
administered were
and
minimal.
the
ACKNOWLEDGMENTS
The
I should like to express my appreciation to Dr.
value o f this agent in ophthalmology f> i^J appears to be in the treatment o f acute epi-
""'i Eduardo Lopez for their assistance m the conduct of this investigation.
chief
observed
Ϊ^Γ'^'/ f
°.^""¡f ^'^ Ρ';
REFERENCES
1. Cantonnet, Α . : Essai de traitement du glaucome par les substances osmotiques. Arch. Ophtal., 24:1, 1904. 2. : Variations de volume de I'oeil sain ou glaucomateux sous I'influence des modifications de la concentration moleculaire du sang. Arch. Ophthal., 24 :193, 1904. 3. Hertel, Ε . : Experimentelle Untersuchungen über die abhangigkeit des augendrucks von der blutbeschaflfenheit. Arch. f. Ophth., 88:197, 1914. 4. Dyar, E. W . , and Matthew, W . B.: Use of sucrose preparatory to surgical treatment of glaucoma. Arch. Ophth., 18:57, 1937. 5. Bellows, J., Puntenney, I., and Cowen, J.: Use of sorbitol in glaucoma. Arch. Ophth., 20:1036, 1938. 6. Bárány, Ε. Η . : Influence of gum arabic (acacia) and dextran on the blood-aqueous barrier and intraocular pressure. Ophthalmologica, 116:65, 1948. 7. Dawson, H., and Thomassen, Τ. L . : The effect of intraveous infusion of hypertonic saline on the intraocular pressure. Brit. J. Ophth., 34:3S5, 1950. 8. Barry, K. G., and Berman, A. R.: Mannitol Infusion: III. The acute effect of the intravenous in fusion of mannitol on blood and plasma volumes. New England J. Med., 264:1038, 1962. 9. Wise, B. L., and Chater, Ν . : The value of hypertonic mannitol solution in decreasing brain mass and lowering cerebrospinal-fluid pressure. J. Neurosurg., 19:1038, 1962. 10. Cheney, F. W . , Jr., and Lincoln, J. R.: Mannitol therapy: Current status. J. Maine M. Α., 5 4 : 172, 1963. 11. Weiss, D. L., Shaffer, R. N., and Wise, B. L . : Mannitol infusion to reduce intraocular pressure. A M A Arch. Ophth., 68:341, 1962. 12. Smith, E. W . , and Drance, S. M . : Reduction of human intraocular pressure with intravenous mannitol. A M A Arch. Ophth., 68:734, 1962. 13. Adams, R. E., Kirschner, R. P., and Leopold, 1. H . : Ocular hypotensive effect of intravenously administered mannitol. A M A Arch. Ophth., 69:89, 1963. 14. Galin, M. Α., Davidson, R., and Pasmanik, S.: An osmotic comparison of urea and mannitol. Am. J. Ophth., 55 :244, 1963. 15. Weiss, D. I., Shaffer, R. N., and Harrington, D. O . : Treatment of malignant glaucoma with intra venous mannitol infusion. A M A Arch. Ophth., 69:154, 1963. 16. Kwitko, M. L., and Costenbader, F. D . : Glaucoma due to secondary hyphema. Am. J. Ophth., 53 :590, 1962. 17. Hill, K., Whitney, T. B., and Trotter, R. R . : Intravenous hypertonic urea in the management of acute angle-closure glaucoma. A M A Arch. Ophth., 65 :497, 1961. 18. Barry, K. G., and Malloy, J. P.: Oliguric renal failure: evaluation and therapy by the intravenous infusion of mannitol. J.A.M.A., 179:510, 1962. 19. Boba, Α., Gainor, J., and Powers, S. R., Jr.: The influence of mannitol on water and electrolyte excretion following trauma. Surgery, 52 :188, 1962. 20. Wood, C , and Borges, F. J.: Toxicity associated with mannitol adininistration, Mannitol Sym posium. Walter Reed Army Institute of Research, Washington, D.C. February 3, 1962, p. 25.
HILL,
MANNITOL
M.D.
Waterville, Maine CHjOH I HOCH I HOCH
The use o f osmotic agents to lower intraocular pressure dates back to the investigations o f Cantonnet^'^ and Hertel.' Several osmotically active substances*'^ have been tried through the years but they have not been entirely satisfactory. Recently, intravenous hypertonic urea has been used extensively but it, too, is not without disadvantages.
HCOH
I
intervals thereafter. T h e same Schiøtz tonometer was used and the readings were converted on the basis o f the 1955 scale. All patients were observed and questioned f o r sideeffects and, in most instances, a special note was made o f the approximate depth o f the anterior chamber.
RESULTS
T h e patients to w h o m mannitol infusions were given can be divided into four groups, based upon the particular clinical problem which each patient presented: 1. Angle-closure glaucoma. Five patients presented with high ocular tension due to acute closure of the anterior chamber angle. T h e diagnosis was confirmed b y gonioscopy in all cases. It is interesting that three o f the patients developed acute angle closure while receiving miotics. A fourth case was treated initially with pilocarpine, eserine and acetazolamide without a satisfactory lowering o f ocular tension.
Mannitol solution f o r intravenous use is readily available and does not require mixing prior to administration. Prewarming the solution to prevent crystallization at room temperature has been recommended but this has not been routinely necessary in the present study. MATERIALS
T h e dosage o f mannitol administered to these patients varied (table 1) but in all instances there was a prompt fall in ocular tension which was maintained by miotics or carbonic anhydrase inhibitors until glaucoma surgery could be performed (fig. 2 ) . T h e depth and gonioscopic appearance o f the anterior chamber was observed in four cases after the ocular tension had been lowered
All patients in the study received an intravenous infusion o f 20-percent mannitol solution.* Fluids were denied the patients during the infusion period. The ocular tension was determined immediately before the infusion was started and at various short * Kindly supplied by Martin McGaw Laboratories, Inc.
Roberts,
Milliosmoles/100 gm. = S49
CHjOH Fig. 1 (Hill). The structure of mannitol.
Mannitol is a 6-carbon hexahydric alcohol (fig. 1 ) which is stable in solution. A d ministered intravenously, it is distributed throughout the extracellular fluid compartment and is not significantly metabolized by the body. It is rapidly and totally excreted b y filtration through the renal glomeruli and is not reabsorbed by the tubules.
A N D
Distribution; Extracellular fluid compartment.
HCOH
Because o f the continuing search f o r an effective ocular hypotensive agent without side-effects, a clinical investigation of mannitol has been undertaken during the past 18 months. T h e usefulness o f mannitol in other fields of medicine has been well documented'"^" and a few reports o f the ophthalmic uses of this agent have already appeared.^^"^'
METHOD
Molecular VVeight = 182.17
Ph.D., 79
80
KEVIN
HILL
TABLE 1 DOSAGE OF 20 PERCENT MANNITOL AND ASSOCIATED SIDE-EFFECTS Mannitol Dosage tictac
Side-Effects
i>υ.
gm./kg.
gm./kg./hr.
ml./min.
1.00 1.80 3.10 1.67 0.66
1..« 1.00 2.00 3.34 2.64
9.0 5.0 10.5 16.7 16.7
None None Chilly sensation None None
1.03 1.85
1.03 2.47
5.0 11.1
None Mild headache
0.75 0.70 1.60 1.60 1.76 0.90 1.20
1.12 1.40 3.20 3.20 2.63 1.35 1.60
7.5 10.0 13.3 13.3 16.7 9.0 10.0
None None None None None None None
1.40
0.93
6.25
.None
Angle-closure Glaucoma 1 2 3 i 5 Secondary Glaucoma 6 7 Dangerous Eyes 8 9 10 11 12 13 14 Hyphema IS
CASE NUMBER
Fig. 2 (Hill). The effect of 20-percent mannitol on the ocular tension in acute angle-closure glau-
* The numbers at the top of the columns in Figures 2, 3, 4 and 5 indicate the percentage fall in ocular tension.
by mannitol and n o change from the preinfiision examination was noted. 2. Secondary glaucoma. T w o patients with open-angle glaucoma and anterior uveitis pre sented with elevated ocular tension which was not satisfactorily lowered b y intensive topical anti-inflammatory therapy (atropine and corticosteroids) and carbonic anhydrase inhibitors. It is possible that the local steroids may have contributed to the intractability o f the glaucoma in these cases but this was not definitely proved. Mannitol infusions (table 1) promptly lowered the ocular tension in both patients (fig. 3 ) despite the presence of a partially "broken-down" blood-aqueous barrier, as evidenced b y the presence o f cells and flare in the anterior chamber in Case 6 and a flare without cells in the anterior cham ber in Case 7. 3. "Dangerous eyes" undergoing cataract surgery. These patients were mostly younger middle-aged adults with dense pos terior subcapsular cataracts with the possi bility o f a firm adhesion o f the posterior cap sule to the hyaloid. Some of them also had
81
OCULAR OSMOTHERAPY W I T H MANNITOL
UREA O.agm./kg.
•
UREA 1.3gin./ttg.
I n i t i a l ocular tension
I
Ocular t e n s i o n at end o f mannitol Infualon
Ocular TeneIon
MANNITOL 1.4gni,/kq.
CASE NUMBER
Fig. 3 (Hill). The effect of 20-percetit mannitol on the ocular tension in secondary glaucoma.
the heavy-set, bull-necked physique, promi nent eyes and tight lids which are associated with the increased likelihood of vitreous loss. A mannitol infusion was started 30 to 45 minutes before cataract surgery (table 1 ) . In all instances, the ocular tension fell to low levels (fig. 4 ) and cataract extraction was uneventful. 4. Hyphema and secondary glaucoma. Following cataract extraction, a patient de veloped iris prolapse which required repair of the wound. Subsequently, a nearly total hyphema with secondary glaucoma de veloped. The tension was not satisfactorily lowered by large oral doses o f acetazolamide and early hemosiderosis o f the cornea was noted. Because of the apparent beneficial ef fects of intravenous hypertonic urea upon hyphema reported by Kwitko,'^ an infusion of 30-percent urea solution was adminis tered. T h e ocular tension promptly fell but no significant change in the blood clot within the anterior chamber was noted. A repeat
I n i t i a l ocular
Fig. 5 (Hill). The effect of 30-percent urea and 20-percent mannitol on ocular tension in hyphema (Case 1.Í).
infusion o f urea on the following day also lowered the ocular tension but was without obvious eifect upon the hyphema. Four days later, with little change in the hyphema and with recurrence o f increased ocular tension, an infusion o f 20-percent mannitol was given. Again, there was a prompt fall in ocular tension but n o visible effect upon the clot.. Subsequently, the clot was removed surgically with the aid o f fibrinolysin. T h e ocular hypotensive effects o f urea and mannitol in this patient are sum marized in Figure 5. O f interest is the fact that during both urea infusions administered through differ ent antecubital veins, a moderate burning sensation at, and proximal to, the needle site was noted by the patient. T h e infusion needles were tested and thought to be well positioned in the vein. A f t e r the first urea infusion, a mild phlebitis developed. The subsequent administration of maimitol was without any noticeable effect upon the vein.
• Fig. 4 (Hill). The effect of 20percent mannitol on the ocular ten sion in nonglaucomatous patients undergoing cataract surgery.
mm. Hg. schletz
O c u l a r t e n s i o n a t end mannitol infusion
of
KEVIN HILL
82
minutes, and the duration o f effect is approx
SIDE-EFFECTS
A s summarized in Table 1, the side-effects associated with the intravenous administra tion of mannitol were mild and few. Head ache and chilis appear to be the most fre quently occurring side-effects reported thus far. It should be noted that in some patients with acute angle-closure glaucoma, headache is relieved by the reduction o f ocular tension during
mannitol
infusion.
Other
reported
side-effects o f mannitol, such as dizziness, rhinitis, urinary retention, nausea, phlebitis and chest pain,""^^ were not noted in the present series. Accidental extravasation o f mannitol has occurred at the
infusion
site and,
unlike
urea, has not produced severe tissue necrosis. Although irritation of veins by 20-percent mannitol has been reported, the comparative obser\'ations already noted suggest that man nitol is less irritating than urea in this re spect. Other disturbing side-effects, such as severe back pain and disorientation
which
have been described f o r urea,^' have not, as yet, been observed following mannitol
ad
ministration.
imately five to seven hours depending upon the state of the blood-aqueous barrier and the fluid intake o f the patient. F o r most patients in w h o m the achievement o f ocular hypoten sion is desirable, a dosage o f I.O or 2.0 g m . / kg. administered in 30 to 60 minutes appears to be satisfactory. F o r those cases, such as the patients undergoing cataract surgery in whom the initial ocular tension is not high, a lower total dose will be necessary to achieve a satisfactory hypotensive effect. A reason able rate f o r the infusion o f the 20-percent mannitol solution is 10 ml./min.,
although
considerably more rapid rates o f administra tion have been well tolerated (table 1 ) . Personal experience in the use o f both agents bears out the impression o f other in vestigators that mannitol has certain advan tages over urea. Mannitol does not elevate the blood urea nitrogen content and thus is preferable in patients with poor renal func tion.'' It is not significantly metabolized b y the body and can be used safely in patients who must restrict their consumption o f car bohydrates. The side-effects observed thus far appear to be less troublesome than those
CO.MMENT
of urea. F o r example, mannitol appears to
In this series of cases, a 20-percent solu tion o f mannitol proved to be an effective ocular hypotensive agent. Like urea, manni tol lowers ocular tension by virtue o f its o s motic effect. Blood osmolality studies"' indicate the close correlation between changes in blood osmolality and ocular ten sion. Careful gonioscopy in cases of acute angle-closure glaucoma indicates that the hy potensive effect of mannitol is not dependent upon reopening o f the usual channels for aqueous outflow, f o r the ocular tension is lowered despite obvious continued closure of the anterior chamber angle. In some in stances, deepening o f the anter'or chamber after mannitol infusion has been reported'^ but careful observation o f the present series of patients could not confirm this.
be less injurious than urea when it is extrav-
The hypotensive action o f mannitol is prompt, a definite effect appearing within 30
sibility of untoward effects should be con
asated. Mannitol solution is also more stable and does not require the bothersome prepara tion necessary with urea. This is not to say that hypertonic manni tol solution is entirely innocuous. T h e rapid administration of large doses of mannitol to patients with cardiac failure or low cardiac reserve, especially if renal function is im paired, may be hazardous due to rapid e x pansion o f the extracellular fluid space and consequent overloading o f the cardiovascular system.
Electrolyte
imbalance
may
result
from the sodium diuresis caused by mannitol infusion."'-" mannitol
Repeated
administration
( o r any osmotic agent)
of
without
adequate fluid replacement could lead to a marked state of hyperosmolarity. T h e pos sidered and all patients receiving intravenous
OCULAR OSMOTHERAPY W I T H MANNITOL
83
mannitol should be carefully evaluated before
sodes o f glaucoma (angle-closure, malignant,
and
and secondary types) and in the preoperative
observed during administration o f this
agent.
preparation o f
certain patients
cataract extraction in w^hom the
S U M M A R Y
. c cc roo T h i s study confirms the emcacy o f ZO-per-
undergoing danger o f
vitreous loss appears likely. ^^^^ ^ Avenue
cent mannitol as an ocular hypotensive agent in a variety o f clinical ophthalmic conditions. Mannitol side-effects
is
easily
administered were
and
minimal.
the
ACKNOWLEDGMENTS
The
I should like to express my appreciation to Dr.
value o f this agent in ophthalmology f> i^J appears to be in the treatment o f acute epi-
""'i Eduardo Lopez for their assistance m the conduct of this investigation.
chief
observed
Ϊ^Γ'^'/ f
°.^""¡f ^'^ Ρ';
REFERENCES
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