administered orally.24 The intravenous drugs are usually administered over a period of 45–60 minutes.

Mannitol

Mannitol (Osmitrol) is an effective hyperosmotic drug that is currently the agent of choice for intravenous administration.The usual dose is 2.5–7.0 ml/kg of the 20% solution (see Table 28-1). The drug begins to lower IOP in 15–30 minutes, reaches a maximum

effect in 30–60 minutes, and has a duration of action of approximately 6 hours.30,36–38 It is not necessary to administer the full dose

of the drug; when IOP falls to the desired level, the infusion can be terminated. Mannitol is excreted unchanged in the urine (i.e., it is not metabolized). Because it penetrates the eye poorly, mannitol is especially useful as a hypotensive agent in the presence of ocular inflammation.24 The 20% solution is stable and less irritating to blood vessels and subcutaneous tissue than is urea.36

The major disadvantages of mannitol are the greater likelihood of cellular dehydration because of its confinement to extracellular water and the larger volume of fluid required because of its limited solubility.39 Cellular dehydration in the CNS may produce symptoms of dementia and disorientation, especially in the elderly. Great caution should be observed in patients with renal failure because they may be unable to excrete the large quantity of fluid extracted from the cells. Similarly, the increased blood volume may place an intolerable load on patients with congestive heart failure.The 20% solution should be warmed to dissolve crystals, and a blood administration filter should be used in the intravenous line. An anaphylactic reaction to mannitol has been reported.40

Urea

Urea (Urevert, Ureaphil) was the first intravenous agent used for the treatment of glaucoma. Administered intravenously as a 30% solution in a dose of 2.0–7.0 ml/kg (see Table 28-1), urea begins

to lower IOP in 15–30 minutes, reaches a maximum effect in 60 minutes, and has a duration of action of 4–6 hours.41–44 Urea is

slightly less effective than is mannitol because urea diffuses more freely through body water and penetrates the eye more readily.The latter is especially true in inflamed eyes.23 The drug is prepared in a 10% invert sugar solution to prevent hemolysis. Urea is not metabolized and is excreted rapidly in urine.

As urea is cleared from the circulation, the plasma osmolality may fall below that of the vitreous, resulting in a rebound increase in IOP. Only fresh urea solutions should be administered because old solutions decompose to ammonia. However, fresh solutions must be warmed to compensate for the endothermic reaction of dissolving the drug. The physician should be aware that warming the solution to 50°C or higher produces ammonia. Extravasation of urea results in thrombophlebitis and skin necrosis.43 Because of these side effects, urea is rarely used.

Side effects

Side effects from hyperosmotic agents are relatively common (Box 28-1).Although most of the associated side effects are relatively mild, some are serious and even potentially fatal. These drugs should be administered with caution in patients with cardiac, renal, and hepatic disease. Headache, nausea, vomiting, and diuresis are the most fre-

quent side effects and are seen with all of the agents in clinical use.29,43 Intense diuresis after hyperosmotic therapy may lead to uri-

nary retention and a need for catheterization, especially in older men

Box 28-1  Side effects of hyperosmotic agents

Gastrointestinal

Nausea

Vomiting

Diarrhea

Abdominal cramping

Cardiovascular

Angina

Congestive heart failure

Pulmonary edema

Central nervous system

Headache

Backache

Confusion

Disorientation

Chills

Fever

Subdural hematoma45

Renal/genitourinary

Diuresis

Loss of potassium

Urinary retention

Anuria46

Miscellaneous

Arm pain

Skin slough

Thrombophlebitis

Acidosis

Diabetic ketoacidosis

Hyperosmolar non-ketotic coma27

Urticaria

Laryngeal edema

Anaphylactic reaction

Hyphema

Suprachoroidal hemorrhage

with prostatic enlargement. Nausea, vomiting, and a desire to void may interfere with the calm conditions desired for surgery. For this reason, patients should void before coming to the operating room.

Hyperosmotic agents, especially those restricted to extracellular water, may precipitate pulmonary edema and congestive heart failure in elderly patients with borderline cardiac and renal status. In patients with borderline or poor renal function, acute renal failure may be precipitated by intravenous agents.45,47 Cellular dehydration, including cerebral dehydration with resulting disorientation, is also more common with agents limited to the extracellular space. Subdural hematoma is a life-threatening complication that occurs when shrinkage of the cerebral cortex stretches and ruptures aqueous veins between the sagittal sinus and the brain surface.48 Many of the serious side effects are dose related, so patients should receive the minimum dose necessary to reduce IOP to the desired level.

Suggestions for clinical use

With the availability of many new topical agents, the need for hyperosmotics has declined significantly. However, they may be useful in some acute situations in which topical agents and systemic carbonic anhydrase inhibitors are unable to control IOP.