Medical Treatment: Osmotic Agents

Core Messages

››Intravenous mannitol and oral glycerin (glycerol) can be used for the rapid reduction of elevated intraocular pressure (IOP) in emergency situations.

››Hyperosmotics can be used to lower IOP before surgery so as to minimize certain intraoperative and postoperative complications that are associated with rapid reductions of very high IOP.

››Hyperosmotics should be avoided in patients with cardiac, pulmonary, or renal dysfunction­.

››Oral glycerin should be avoided in diabetics.

osmotic agents formerly used – isosorbide, alcohol, and urea – have comparable efficacy to mannitol and glycerin but were seldom used because of worse side effect profiles. However, even the currently used osmotics have potentially life-threatening side effects, and they should be used with caution (see Sect. 27.2).

Mannitol can be given either as an IV infusion or IV push. For IV infusion, mannitol may be purchased premixed in 250or 500-ml bags (Fig. 27.1; mannitol 20%, Hospira Worldwide Inc., Lake Forest, IL; mannitol 20%, B. Braun Medical Inc., Sheffield, United Kingdom; osmitrol 20%, Baxter Medication Delivery, Deerfield, IL). For IV push, mannitol (mannitol 25%, American Regent Inc., Shirley, NY) can be purchased as 50-ml

27.1  When Using Hyperosmotics Agents, What Is a Typical Dose for Acutely Elevated Intraocular Pressure (IOP)?

Hyperosmotic agents, or osmotics, are generally used for short-term IOP control in emergency situations [1] where other medications are unable to lower the IOP [2]. Intravenous (IV) mannitol and oral glycerin (or glycerol) are the most commonly used hyperosmotic agents [1, 3]. Both agents penetrate the blood–ocular barrier poorly, which is a definite advantage, since this fact creates a larger osmotic gradient for water to follow. Other

T. C. Chen ( )

Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

e-mail: teresa_chen@meei.harvard.edu

Fig. 27.1  500 ml of 20% mannitol in a plastic bag for intravenous infusion

Fig. 27.2  50 ml of 25% mannitol in a single-dose vial for intravenous push

single-dose vials (Fig. 27.2). Because of the limited solubility,­ storage at room temperature (25°C) is recommended. Mannitol solutions commonly crystallize at low temperatures. If crystallization occurs (Fig. 27.3), the solution should be warmed prior to use. Mannitol should not be administered if crystals are present.

Mannitol is typically administered as an IV infusion using a 20% premixed solution (concentration of 200 mg/ml) at a dose of 1–2 g/kg of body weight [3, 4]. The authors prefer the lower dose of 1 g/kg, which works sufficiently in our experience. Mannitol should be administered intravenously over 30–60 min. Too rapid an infusion of mannitol will cause a shift of intracellular water into the extracellular space, resulting in cellular dehydration with a high risk of hyponatremia, congestive heart failure, and pulmonary edema. Slow administration, over at least 20–30 min, may also avoid transient increases in cerebral blood flow that may exacerbate or increase intracranial bleeding in predisposed patients. Doses in excess of 200 g IV mannitol/day have been associated with acute renal failure.

Although the indications are very rare, mannitol may be administered as an IV push over 3–5 min as a 25% injection. Use of mannitol IV push should be reserved for cases where more conservative medical treatments do not lower extremely elevated eye pressures and when an emergent laser or surgical treatment is not possible. The benefits of immediate eye pressure reduction must always be weighed against the significant general medical risks of IV push, and the IV push route is preferably administered by a physician for the reasons noted above. IOP reduction can be seen within 45 min of administration and can last up to 6 h [3]. Peak effect is seen 1–2 h after administration [2].

Fig. 27.4  Glycerin oral solution that is prepared according to a recipe from the Massachusetts Eye and Ear Infirmary, Harvard Medical School

Glycerin (or glycerol) is usually used as a 50% oral solution at a dose of 1–1.5 g/kg of body weight [3, 5, 6]. Because of its unpleasantly sweet taste, it is often given with juice or over ice [7]. The onset of effect can occur within 10 min, with a peak effect at approximately 1 h [3, 8]. The duration of action is 4–5 h. In elderly patients, the minimum dose (e.g., 1 g/kg) required to produce the desired effect should be used to avoid serious side effects.

Glycerin was commercially available as Osmoglyn (50% solution, 220-ml bottle by Alcon Laboratories Inc., Fort Worth, TX); however, it is no longer marketed in the United States. We mix our own solution (Fig. 27.4) and use the following recipe for oral glycerin 50% (courtesy of the Massachusetts Eye and Ear Infirmary Department of Pharmacy). The expected yield of this recipe is 900 ml (Table 27.1). The ingredients are Crystal Light™ (a powdered sugar-free drink mix, Kraft Foods, Inc., Northfield, IL), sterile water for irrigation (900 ml), and glycerin USP (450 ml, Humco, Texarkana, TX). The solution can be stored for up to 3 months in a refrigerator. The usual dosage is 2–3 ml of glycerin solution/kg of body weight (approximately 4–6 oz/individual). Glycerin solution can be used in the cardiovascular or severely dehydrated­

patient with contraindications to mannitol. Isosorbide (Ismotic, no longer marketed in the United States) had been used as an alternative to oral glycerin in patients with diabetes.

The typical dosage and side effects for mannitol and glycerin are summarized in Table 27.2 [1, 5, 6, 9, 10]. Since osmotics are used for the temporary or immediate control of elevated IOP and not for long-term pressure control, the typical dosage of these agents is for onetime use. Repeat administration of osmotics without adequate fluid replacement may lead to a marked state of hyperosmolarity and cellular dehydration, which can result in severe headache, disorientation, and confusion from cerebral dehydration [4]. Although there has been a report of daily administration of oral glycerin for 50 days without evidence of toxicity, long-term therapy and repeat administration of these agents are not recommended [6].

Summary for the Clinician

››Mannitol may be given as an IV infusion (20% mannitol) at a dose of 1–2 g/kg of body weight over 30–60 min.

››In truly emergent situations of elevated IOP, an IV push of 25% mannitol injection can be given over 3–5 min by a physician.

››Oral glycerin may be given as a 50% solution at a dose of 1–1.5 g/kg of body weight, with juice or over ice. The usual dosage is 2–3 ml of 50% glycerin/kg of body weight (approximately 4–6 oz/individual).

››Hyperosmotic agenvts can be used to rapidly lower the IOP for one-time usage, but osmotics are not recommended for long-term use.

››In elderly patients, use the minimum dose required to produce the desired effect.

27.2  What Systemic History Should

I Gather Prior to Administering

Hyperosmotic Agents?

which may then lead to seizures and coma. In diabetic patients, oral glycerin should be avoided, because it is metabolized to glucose, which can lead to serious hyperglycemia and possibly ketoacidosis. Cellular dehydration, including cerebral dehydration with resultant headache and disorientation, may occur more often with mannitol [3, 10]. Intracranial hemorrhage has also been reported with the use of mannitol [11].

Summary for the Clinician

››Rapid IV infusion of hyperosmotic agents leads to rapid shifts of intracellular water that can lead to hyponatremia, congestive heart failure, and pulmonary edema.

››Hyperosmotics, especially mannitol, are contraindicated in renal failure.

››In patients with compromised cardiac function, the use of hyperosmotics should be restricted.

››Oral glycerin is metabolized to glucose and therefore should be avoided in diabetic patients.

››Intracranial hemorrhage has been reported with IV mannitol.

Osmotics are contraindicated in certain systemic conditions, and so past medical history and review of systems must be thorough and include questions regarding cardiovascular status, renal function, diabetes mellitus, and recent water intake.

Because hyperosmotic agents increase the extracellular space, they may precipitate pulmonary edema and cardiac failure in patients with compromised cardiac function [1, 3, 5, 10]. Osmotics should be avoided or used very cautiously in patients with cardiac conditions. These agents are contraindicated in patients with renal failure [1, 3], especially mannitol, as they may induce diuresis and resultant electrolyte imbalance,

Table 27.2  Characteristics of mannitol and glycerin (glycerol)

27.3  Should Hyperosmotic Agents Be Used to Lower IOP Prior to Surgery?

Osmotics have been used to reduce IOP before various types of intraocular surgery [1–3, 5, 7, 12–14]. Only a minority of clinicians advocate the routine use of preoperative hyperosmotic agents. These proponents feel that hypotony and vitreous dehydration are desirable before cataract extraction, corneal transplantation, repair of corneal lacerations, or retinal detachment surgery­ [5]. A majority of clinicians, however, would consider using