Anesthesia for ophthalmic surgery

Introduction

Uncorrected ophthalmic problems can impair child development, interfere with learning, and even lead to permanent vision loss, so early detection and treatment are critical ( ). An examination under anesthesia (EUA) is often necessary for diagnosis, especially in infants or uncooperative children. Anesthesia for ophthalmologic procedures in infants and children is essential for optimal diagnosis and intervention. Because ophthalmologic procedures range in complexity from exams under anesthesia to invasive cataract, glaucoma, and retinal surgeries, the pediatric anesthesiologist will require an understanding of several physiologic and pharmacologic concepts that are unique to this population in order to provide the best care. The information contained in this chapter will give anesthesiologists the information needed to plan for and safely perform anesthesia for pediatric ophthalmic procedures. A glossary of useful terms is given in Box 37.1 .

BOX 37.1

Glossary of Ophthalmologic Terms

Blepharospasm: Tonic spasm of the orbicularis oculi muscle, producing more or less complete closure of the eyelids
Buphthalmos: Enlargement and distention of the fibrous coats of the eye
Cyclocryotherapy: Freezing of the ciliary body, performed for the treatment of glaucoma
Epiphora: Abnormal overflow of tears, also known as illacrimation
Episcleritis: Inflammation of tissues overlying the sclera, also inflammation of the outermost layers of the sclera
Gonioscopy: Examination of the angle of the anterior chamber of the eye
Goniotomy: Operation for glaucoma characterized by an open angle and normal depth of the anterior chamber; consists of the opening of Schlemm’s canal under direct vision secured by a contact glass
Tonometry: Measurement of tension or pressure commonly assessed by the applanation
Tonometer: Instrument that measures intraocular pressure by determination of the force necessary to flatten a corneal surface of constant size
Trabeculectomy: Creation of a fistula between the anterior chamber of the eye and the subconjunctival space by surgical removal of a portion of the trabecular meshwork

From Dorland’s illustrated medical dictionary . (2000). Philadelphia: Saunders.

Anesthesiologists with a particular interest in ophthalmologic anesthesia can find valuable resources through the Ophthalmic Anesthesia Society ( http://www.eyeanesthesia.org ) and the British Ophthalmic Anaesthesia Society ( http://www.boas.org ).

Epidemiology

There were approximately 4000 eye operations on patients younger than 15 years of age who were admitted in 2010 ( ). Similarly, 4778 eye procedures were performed in 2012 on inpatients younger than 17 years of age ( ). For outpatients, the National Survey of Ambulatory Surgery estimates that in 2006 there were approximately 103,000 eye procedures performed on patients younger than 15 years of age ( ). It is evident that most pediatric ophthalmologic procedures are performed in the ambulatory setting.

In an analysis of ophthalmic procedures performed in surgery centers, the reasons for cancellation of surgery within 24 hours were explored. The pediatric group (0 to 9 years of age) had the highest rate of cancellation compared with those in other age groups. The majority of cancellations, however, were because of unpreventable causes such as patient illness ( ).

Anatomy and physiology

Knowledge of the anatomy and physiology of the eye is paramount to understanding the array of ophthalmic procedures performed, the influence that anesthesia may have on normal and abnormal ocular physiology, and the systemic effects that surgical manipulation of the eye may have on the patient ( ).

Anatomy

The eye is an extension of the central nervous system (the diencephalon) that rests in the orbit, is cushioned by fat, and is suspended by ligaments and fascial structure.

The orbit is formed by a complex arrangement of seven cranial bones: frontal, zygomatic, sphenoid, maxilla, palatine, lacrimal, and ethmoid ( Fig. 37.1 ). The optic foramen transmits the optic nerve, the ophthalmic artery and vein, and the sympathetic contributions from the carotid plexus. The superior orbital fissure transmits branches from four other cranial nerves (oculomotor, trigeminal, trochlear, and abducens) and the superior and inferior ophthalmic veins. The infraorbital fissure (representing the weakest aspect of the orbit) transmits the infraorbital and zygomatic nerves. The infraorbital foramen (located below the orbital rim) transmits the infraorbital nerve, artery, and vein.

Fig. 37.1, Skeletal Anatomy of the Orbit.

The globe is composed of three contiguous layers: the sclera, uveal tract, and retina. The sclera is the dense outer covering that provides the fibrous structure necessary for maintaining the shape of the globe. Anteriorly the sclera is replaced by a transparent, avascular layer called the cornea, which permits transmission of light to the retina. The highly vascular uveal tract is composed of the iris, ciliary body, and choroid, enveloping the posterior aspect of the globe. The iris acts as the posterior-most landmark of the anterior chamber and is filled with aqueous humor. The ciliary body is the site of aqueous humor production and contains the ciliary muscles that are responsible for accommodation of the lens. The choroid is the highly vascular layer of the globe that provides blood supply to the retina. The retina is a delicate membrane composed of ten distinct layers that are involved in the conversion of light to neural impulses. The axons of the retinal ganglion nerves converge at the optic disc and pierce the sclera to form the optic nerve.

The aqueous humor occupies the anterior and posterior chambers (area between the posterior surface of the iris and the anterior surface of the lens) of the eye and is responsible for providing nutrients to the avascular lens and the endothelial aspect of the cornea ( Fig. 37.2 ). The volume of aqueous humor (0.3 mL in the adult) is primarily responsible for intraocular pressure (IOP) regulation. The vitreous humor, created embryologically between 1 and 4 months’ gestation, is a hydrophilic gel that accounts for 80% of the volume of the globe. The vitreous humor is 99% water, although in the presence of hyaluronic acid (a mucopolysaccharide) its viscosity is twice that of water. The volume of the vitreous humor is more constant than that of the aqueous humor, although it may be slightly influenced by hydration status and osmotically active medications. The vitreous humor sits between the lens and the retina in the posterior segment of the eye.

The optic nerve (cranial nerve II) is the nerve of vision and may be thought of as a diverticulum of the forebrain. The oculomotor nerve (cranial nerve III) provides motor innervation to four of the six extraocular muscles and the levator palpebrae superioris and parasympathetic innervation to the pupillary sphincter (miosis) and ciliary muscles (accommodation). The two other extraocular muscles are innervated by the trochlear (cranial nerve IV) and abducens nerves (cranial nerve VI). The ophthalmic division of the trigeminal nerve (cranial nerve V) transmits all of the nonvisual sensory innervation from the eye and orbit and provides sympathetic innervation to the pupillary dilators (mydriasis). The temporal and zygomatic branches of the facial nerve (cranial nerve VII) innervate the orbicularis oculi ( ).

Blood is supplied to the eye and orbit through branches of the internal and external carotid arteries. The first branch of the intracranial carotid artery, the ophthalmic artery, divides into the central retinal artery, as well as the long and short posterior ciliary arteries, to nourish the retina. The long and short posterior ciliary arteries converge to supply the choriocapillaris, the capillary layer within the choroid that supplies 60% to 80% of the oxygen to the retina. The anterior portion of the optic nerve is perfused by the posterior ciliary arteries. This network of arteries is subject to significant individual variation, predisposing some patients to anterior ischemic optic neuropathy after periods of hypotension. The posterior optic nerve is perfused by pial vessels branching from the ophthalmic artery. Superior and inferior ophthalmic veins drain the orbit, and the central retinal vein provides ocular drainage. All venous drainage is subsequently transmitted to the cavernous sinus ( ).

Physiology

Intraocular pressure

The physiology of the eye is quite complex, but an understanding of the physiologic and pharmacologic control of IOP is of primary importance to the anesthesiologist. The ability to avoid deviations in IOP is key to providing satisfactory anesthesia for all intraocular procedures and in caring for the patient with glaucoma and traumatic injury to the globe.

Normal IOP varies between 10 and 20 mm Hg and may differ by as much as 5 mm Hg between the two eyes. Normal pressures are somewhat lower in the newborn (average, 9.5 mm Hg) but become approximately adult pressures by 5 years of age ( ). A pressure above 25 mm Hg at any age is considered abnormal in the presence of a normal cornea ( ). Transient changes in IOP are well tolerated in the intact eye, although chronic elevations may be detrimental to normal retinal perfusion and vision.

Three primary determinants of IOP are external pressure, venous congestion, and changes in intraocular volume. The volume and exertional pressure of the aqueous humor are carefully regulated in the normal eye to maintain normal IOP. As mentioned earlier, the volume of the vitreous humor is usually constant.

The aqueous humor is formed primarily by the ciliary bodies, where secretion is facilitated by the carbonic anhydrase and cytochrome oxidase systems. The feedback control of aqueous humor formation is poorly understood, although production of aqueous humor is known to be augmented by sympathetic stimulation and suppressed by parasympathetic control. Variations in the osmotic pressure of the aqueous humor and plasma influence aqueous humor formation, as illustrated by the following equation:

I O P = k [(O P a q - O P p l) + P c]

$I O P = k [(O P a q - O P p l) + P c]$

where k is the coefficient of outflow; OPaq and OPpl are the osmotic pressures of the aqueous humor and plasma, respectively; and Pc is the capillary perfusion pressure. The benefit of hypertonic solutions in lowering IOP is realized through an understanding of this equation.

Most of the aqueous humor produced in the posterior chamber flows through the pupil into the anterior chamber, exiting the eye through Schlemm’s canal (a thin vein that extends circumferentially around the eye) and into the orbital venous system.

Fluctuations in aqueous humor outflow also dramatically alter IOP. The prime factor determining outflow of aqueous humor is the diameter of Fontana’s spaces, as illustrated by the following equation based on the Hagen–Poiseuille law:

A = \frac{r^{4} (P i o p - P v)}{8 η l}

$A = \frac{r^{4} (P i o p - P v)}{8 η l}$

where A is the volume of aqueous humor outflow per unit of time, r is the radius of Fontana’s spaces, Piop is IOP, Pv is venous pressure, η is viscosity, and l is length of Fontana’s spaces.

With mydriasis, Fontana’s spaces narrow, resistance to outflow is increased, and IOP rises. Mydriasis is a threat in both closed-angle and open-angle glaucoma. *

* Open-angle glaucoma, also known as chronic simple glaucoma , is a condition of elevated IOP in an eye with an anatomically open anterior chamber angle. The trabecular meshwork is thought to be sclerosed, resulting in inefficient aqueous filtration and drainage. Closed-angle glaucoma is a mechanical closing of the pathway for aqueous egress for the eye. The iris may move into direct contact with the posterior surface of the cornea, impeding the aqueous outflow path, or the crystalline lens may swell, resulting in papillary blocking. In the latter case, the lens blocks the route for aqueous humor to travel from the posterior to the anterior chamber.

Hence, a miotic agent such as pilocarpine hydrochloride is often efficacious when applied conjunctivally before surgery in patients with glaucoma.

Stimulation of α ₁ -sympathetic receptors leads to mydriasis, a decrease in aqueous outflow, and an increase in IOP. Most of the agents used to produce mydriasis also modestly increase IOP, but in children the coincidental posterior shift of the lens–iris diaphragm counteracts any such effect and the IOP does not rise. β-stimulation has no effect on pupillary diameter, but paradoxically, both β agonists and β antagonists may decrease IOP. Cholinergic stimulation or parasympathetic stimulation produces miosis and decreases in IOP such that glaucoma patients are commonly treated with miotic agents ( ).

The arterial circulation of the eye is autoregulated. Only marked deviations in systemic arterial pressures affect IOP. Elevated venous pressures, on the other hand, can dramatically increase IOP, primarily by augmenting the choroidal blood volume and tension of the orbit ( Box 37.2 ). Coughing, vomiting, and the Valsalva maneuver may increase IOP to 40 mm Hg or more. Respiratory acidosis increases IOP, whereas metabolic acidosis has the opposite effect. Conversely, respiratory alkalosis decreases IOP, whereas metabolic alkalosis increases IOP ( ). Hypoxia is capable of increasing IOP by dilating intraocular vessels, whereas hyperoxia appears to decrease IOP ( ). In fact, a study looking at the Pco ₂ and intraocular pressure showed that low Pco ₂ resulted in lower IOP, whereas high Pco ₂ resulted in higher IOP. The authors concluded that the dynamic nature of this change could only be explained by an increase in blood flow and volume in the choroid. This would explain the so-called positive vitreous pressure seen especially in children 4 years and under during intraocular surgery ( ).

BOX 37.2

Factors Influencing Intraocular Pressure

Factors	Effect
Coughing, vomiting, Valsalva maneuver	⇧
Respiratory acidosis, metabolic alkalosis	⇧
Metabolic acidosis, respiratory alkalosis	⇩
Hypoxia	⇧
Hyperoxia	⇩
Marked elevations in systemic arterial pressure	⇧
Elevated venous pressures (by increasing choroidal blood volume)	⇧
Cholinergic or parasympathetic agonists (by causing miosis)	⇩
α-1 Agonists (by causing mydriasis)	⇧
α-2 Agonists	⇩
β agonists and antagonists	⇩
Hypertonic solutions	⇩

Ophthalmic reflexes

Three ophthalmic reflexes that should be recognized by the anesthesiologist caring for the ophthalmic patient include the oculocardiac reflex (OCR), the oculorespiratory reflex (ORR), and the oculoemetic reflex (OER). All three reflexes are elicited by pressure or torsion on the extraocular muscles transmitting afferent impulses through the ophthalmic division of the trigeminal nerve.

The OCR, through its vagal efferent pathway, may manifest as sinus bradycardia, ectopy, and sinus arrest. Death secondary to the OCR in otherwise healthy children has been described ( ; ). A more thorough description of this reflex, prophylaxis, and therapy is provided in the “Intraoperative and Postoperative Complications” section later in the chapter.

The ORR has also been recognized for nearly 100 years but is less often appreciated with the use of controlled ventilation. Through a postulated connection between the trigeminal nerve, the pneumotaxic center of the pons, and the medullary respiratory centers, pressure on the extraocular muscles may result in tachypnea or respiratory arrest ( ). This reflex is not inhibited by the use of atropine or glycopyrrolate. A review of the ORR and its potential for causing hypercapnia and hypoxia (potentially aggravating the OCR) led some investigators to recommend controlled ventilation during strabismus surgery ( ).

The OER is admittedly more theoretic than the other two reflexes but would explain the high incidence of nausea and emesis after strabismus surgery. An association between the OCR and the OER has been demonstrated such that patients who exhibit the OCR intraoperatively are 2.6 times more likely to experience postoperative vomiting than those without OCR manifestations ( ). Anticholinergic therapy does not decrease the incidence of postoperative nausea and vomiting (PONV). Appropriate prophylaxis and treatment of PONV have been studied extensively and are thoroughly reviewed later in this chapter.

General considerations in caring for the ophthalmologic patient

The anesthesiologist caring for the ophthalmologic patient should be familiar with the disorders and syndromes commonly associated with ocular pathology, the effects of ophthalmic medications used preoperatively and intraoperatively, and the ocular effects of the anesthetic agents to be used during the perioperative period.

Associated congenital and metabolic conditions

Ophthalmologic disorders may be inherited as isolated defects in autosomal recessive, autosomal dominant, and X-linked recessive fashion. A large number of metabolic defects, congenital syndromes, and chromosomal abnormalities are also associated with ocular pathology. The anesthesiologist caring for the ophthalmologic patient must be aware of these associations. An overview of the commonly encountered syndromes and disorders along with their ocular manifestations and potential anesthetic implications is provided in Table 37.1 ( ; ; ).

TABLE 37.1

Congenital Syndromes and Chromosomal Abnormalities with Associated Ocular Manifestations

Disorder or Syndrome	Ocular Manifestations	Anesthetic Implications
Acute intermittent porphyria	Cataracts, retinal degeneration, optic atrophy	Various medications, including barbiturates and etomidate, may trigger attacks.
Apert syndrome	Glaucoma, cataracts, strabismus, hypertelorism, proptosis	Possible difficult intubation, OSA, airway obstruction, possible choanal stenosis, cervical spine fusion, CHD (10% incidence)
Cri du chat syndrome	Strabismus	Micrognathia and possibly difficult intubation, hypotonia, prone to hypothermia, CHD (33% incidence)
Crouzon syndrome	Glaucoma, cataracts, strabismus, hypertelorism, proptosis	Possible difficult intubation, Obstructive Sleep Apnea (OSA), airway obstruction, possible elevated intracranial pressure
Cystinosis	Corneal clouding, retinal degeneration	Chronic renal failure, possible diabetes mellitus, esophageal varices, recurrent epistaxis, hyperthermia
Down syndrome	Cataracts, strabismus	Trisomy 21, airway obstruction, atlantoaxial instability, CHD (50% incidence), may be more sensitive to atropine
Ehlers–Danlos syndrome	Retinal detachment, blue sclera, ectopia lentis, keratoconus	Laryngeal trauma possible with intubation, careful positioning; arterial and central venous lines may cause hematoma and aneurysm
Goldenhar syndrome	Glaucoma, cataracts, strabismus, lacrimal drainage defects	Hemifacial microsomia and possible cervical spine abnormalities, possible difficult mask and intubation, rare CHD, and hydrocephalus
Hallerman–Streiff syndrome	Congenital cataracts, coloboma, microphthalmia, glaucoma	Major craniofacial abnormalities with likely difficult intubation, upper airway obstruction, chronic lung disease
Homocystinuria	Ectopia lentis, pupillary block glaucoma, retinal detachment, central retinal artery occlusion, strabismus, optic atrophy	Marfanoid habitus with kyphoscoliosis and sternal deformity, prone to thromboembolic complications and hypoglycemia
Hunter syndrome	Retinal degeneration, optic atrophy	Often difficult intubation, copious secretions, macroglossia, stiff temporomandibular joint, limited neck mobility, possible ischemic or valvular heart disease
Hurler syndrome	Corneal clouding, retinal degeneration, optic atrophy	Often difficult intubation and difficult mask, possible cervical spine instability, possible ischemic or valvular heart disease
Jeune syndrome	Retinal degeneration	Limited thoracic excursion, pulmonary hypoplasia, possible renal and hepatic insufficiency
Lowe syndrome	Cataracts, glaucoma (hydrophthalmia)	Renal failure, renal tubular acidosis
Marfan syndrome	Ectopia lentis, glaucoma, retinal detachment, cataracts, strabismus	Aortic or pulmonary artery dilation, aortic and mitral valve disease, pectus excavatum, risk for pneumothorax
Moebius sequence	Strabismus, ptosis, congenital nerve VI and VII palsy	Possibly difficult intubation, micrognathia, copious secretions, possible cervical spine anomalies
Myotonia congenita	Cataracts, blepharospasm	Prone to myotonic contractions, sustained contraction with succinylcholine
Myotonic dystrophy	Cataracts, ptosis, strabismus	Prone to myotonic contractions, succinylcholine-associated contractions and hyperkalemia, cardiac conduction abnormalities, sensitive to central nervous system depressants
Rubella syndrome	Cataracts, microphthalmos, glaucoma, optic atrophy	Neonatal pneumonia, anemia, and thrombocytopenia; CHD, hypopituitarism, diabetes mellitus
Sickle cell disease	Retinal detachment, vitreous hemorrhage, retinitis proliferans	Tendency for sickling occurs with high hemoglobin S concentrations, hypoxemia, cold, stasis, dehydration, and infection
Smith–Lemli–Opitz syndrome	Congenital cataracts	Possible difficult intubation, micrognathia, pulmonary hypoplasia, CHD, gastroesophageal reflux, seizure disorders
Stickler syndrome	Vitreous degeneration, retinal detachment, cataracts, strabismus	Possible difficult intubation, micrognathia, mitral valve prolapse, marfanoid habitus, scoliosis, kyphosis
Sturge–Weber syndrome	Choroidal hemangioma, glaucoma, ectopia lentis	Angiomas of the airway, CHD and high output failure, seizure disorders, hyperkalemic response to succinylcholine in those with hemiplegia
Treacher Collins syndrome	Lid defects, microphthalmia	Often difficult intubation, mandibular hypoplasia, CHD
Turner syndrome	Ptosis, strabismus, cataracts, corneal scars, blue sclera	Possible difficult intubation and intravenous access, CHD
von Hippel–Lindau syndrome	Retinal hemangioma	Possible increased intracranial pressure, possible pheochromocytoma, cerebellar tumors may also produce episodic hypertension
von Recklinghausen’s disease (neurofibromatosis 1)	Ptosis, proptosis, optic glioma and meningioma, optic atrophy, glaucoma, Lisch nodules	Possible difficult mask ventilation and intubation, possible airway tumors, restrictive lung disease, renovascular hypertension, possible pheochromocytoma, sensitive to neuromuscular blockers
Zellweger syndrome	Glaucoma, cataracts, optic atrophy, optic nerve hypoplasia	Micrognathia, possible CHD, renal and adrenal insufficiency

CHD, Congenital heart disease; OSA, obstructive sleep apnea.

Ophthalmologic medications and their systemic effects

There are a variety of medications used by pediatric ophthalmologists in the outpatient and perioperative settings that may have important anesthetic ramifications. As with all medications, the ophthalmic agents have both desirable and undesirable effects that may be more pronounced and ominous in the pediatric patient by virtue of greater systemic absorption or higher dosing relative to body weight and pharmacologic compartment. The anesthesiologist must be familiar with every medication used in the perioperative period and pay particular attention to the total dose administered and potential for deleterious effects. An overview of the ophthalmic medications is provided in Table 37.2 .

TABLE 37.2

Commonly Used Ophthalmic Medications

From Duvall, B., & Kershner, R. (2006). Ophthalmic medications and pharmacology (2nd ed.). NJ: SLACK.

Type	Concentration	Pertinent Systemic and Ocular Effects
Cycloplegic (Paralyzes Accommodation)
Cyclopentolate	0.5%, 1%, 2%	Muscarinic antagonist; side effects include gastrointestinal disturbance, atropine-like toxicity, and inhibition of plasma cholinesterase (in vitro).
Tropicamide	0.5%, 1%	Muscarinic antagonist; side effects are minimal.
Atropine	0.5%, 1%, 2%, 3%	Muscarinic antagonist with the most potent ocular effects and a duration of action of longer than 1 week; side effects are numerous.
Homatropine	2%, 5%	Muscarinic antagonist with a shorter onset and duration of action than atropine; side effects are numerous.
Scopolamine	0.25%	Muscarinic antagonist that is not commonly used for diagnostic cycloplegia and mydriasis and for the treatment of iridocyclitis; side effects include an increase in intraocular pressure such that IV or IM scopolamine as a premedication should not be used in the patient with glaucoma.
Mydriatic (Dilates the Pupil)
Phenylephrine	2.5%, 10%	α-Agonist used for maximal mydriasis and vasoconstriction without cycloplegia; potential side effects include hypertension, tachycardia or reflex bradycardia, pulmonary edema, cardiac arrhythmia, cardiac arrest, and subarachnoid hemorrhage.
Hydroxy-amphetamine	1%	Sympathomimetic used in combination with tropicamide primarily for differentiating preganglionic and postganglionic lesions producing Horner syndrome.
Cocaine	4%, 10%	Ester local anesthetic with vasoconstrictive properties; side effects include tachycardia, hypertension, dysrhythmias, hyperthermia, and seizures.
Mydriatic Reversal
Dapiprazole	NA	Sympathomimetic blocking agent that acts by blocking the receptors of the iris dilator muscle. Useful in reversing the dilation induced by mydriatics.
Miotic (Constricts the Pupil)
Acetylcholine	1%	Cholinergic agonist used intraocularly to produce complete miosis after cataract surgery, keratoplasty, other anterior segment surgery; side effects include bradycardia, hypotension, and bronchospasm.
Glaucoma Agent (Direct-Acting Cholinergics)
Pilocarpine	0.25%–10%	Cholinomimetic or parasympathomimetic agent used to produce miosis and a decrease in intraocular pressure for chronic and acute angle-closure glaucoma; side effects include gastrointestinal disturbance, diaphoresis, and brow pain.
Carbachol	0.75%, 1.5%, 2.25%, 3%	Cholinomimetic agent used to produce miosis; more toxic to the cornea with pronounced side effects.
Glaucoma Agent (Indirect-Acting Cholinergics)
Echothiophate iodide	0.125%	Long-acting anticholinesterase agent used to produce miosis for open-angle glaucoma; side effects include bradycardia, hypotension, nausea, vomiting, diarrhea, weakness, and inhibition of plasma cholinesterase for up to 6 weeks after discontinuation.
Physostigmine	0.25%, 0.5%	Weak cholinesterase inhibitor. Only indication is for glaucoma treatment when other miotics have failed.
Glaucoma Agent (Decrease Aqueous Formation)
Timolol, levobunolol	0.25%, 0.5%	Nonselective beta antagonists that reduce intraocular pressure by decreasing aqueous humor production and possibly outflow; side effects include bronchospasm, bradycardia, hypotension, and apnea in neonates.
Betaxolol	0.5%	Selective β ₁ antagonist; side effects are possible but less commonly observed in contrast to the nonselective β antagonists.
Metipranolol	0.3%	Nonspecific β ₁ antagonist; less expensive.
Carteolol	1%	β ₁ Antagonist that does not cross the blood-brain barrier; it has intrinsic sympathomimetic activity and decreased systemic side effects.
Apraclonidine	0.5%, 1%	Selective α ₂ agonist incapable of crossing the blood–brain barrier and used to reduce aqueous secretion; side effects are minimal.
Brimonidine	0.15%, 0.2%	Selective β ₂ agonist capable of crossing the blood–brain barrier; side effects include apnea, bradycardia, hypotension, hypothermia, and somnolence with an incidence as high as 83%.
Acetazolamide	Varies	Systemic competitive inhibitor of carbonic anhydrase that reduces formation of aqueous humor; side effects include acidosis, hypokalemia, hyponatremia, and allergic reactions.
Methazolamide	Varies	Preferred choice when a systemic carbonic anhydrase inhibitor is indicated for glaucoma.
Dichlorphenamide	Varies	Potent carbonic anhydrase inhibitor; high side effect profile.
Dorzolamide, brinzolamide	Varies	Topical carbonic anhydrase inhibitors that reduce the production of aqueous humor; side effects are uncommon.
Glaucoma Agent (Increase Aqueous Outflow)
Epinephrine	0.5%, 1%, 2%	Weak antiglaucoma agent. Stimulates contraction of blood vessels in the ciliary body to reduce aqueous formation. Also increases outflow. Can arouse the sympathetic system.
Dipivefrin	0.1%	Pro-drug of epinephrine. Crosses cornea more easily and is converted to epinephrine in the eye. Can arouse the sympathetic system.
Latanoprost, bimatoprost, travoprost	Varies	Prostaglandin F ₂ analogs that increase aqueous humor outflow and decrease intraocular pressure in open-angle glaucoma; side effects are minimal and usually limited to ocular side effects.
Mannitol	5%–25%	Inert sugar that increases plasma osmotic pressure and decreases the volume of aqueous humor.
Vasoconstrictors (Whiten the Eye)
Naphazoline	0.012%, 0.1%, 0.03%	α-Agonist used primarily for intraoperative vasoconstriction.
Oxymetazoline Tetrahydrozoline	0.025%, 0.05%	Vasoconstrict the superficial conjunctival blood vessels, decreasing redness and irritation; use cautiously in children with vascular disorders.
Analgesics
Proparacaine, tetracaine	0.5%	Ester local anesthetics commonly used intraoperatively and during examination; side effects are minimal and usually limited to burning and possible epithelial damage.
Diclofenac, ketorolac, flurbiprofen, suprofen		Topical NSAIDs are approved for three clinical applications in ophthalmic care: reduction of postoperative inflammation, relief of itching in allergic conjunctivitis, and prevention of pupillary miosis during surgery. Also effective in reducing the pain of corneal surgery. Adverse effects are rare with the exception of stinging with instillation.
Dyes
Fluorescein	0.25%, 2%, 10%, 25%	Dye used to evaluate the integrity of retinal vasculature; side effects include hypertension, nausea, and vomiting.
Rose Bengal	1%	Red-colored dye that specifically binds dead and devitalized tissue. Useful in the diagnosis of corneal and conjunctival damage. Side effects are rare except for stinging with instillation.
Indocyanine Green	NA	Commonly used in ophthalmic angiography and has specific uses in cataract and vitreoretinal surgery. It enables better visualization of the choroidal vasculature. Use with caution in patients with iodine sensitivity; otherwise, reactions are rare.
Trypan Blue	0.06%	Aids in viewing the capsular opening during cataract surgery. Adverse reactions include discoloration of intraocular lenses, but this is self-limiting and of short duration.
Miscellaneous
Sulfur hexafluoride	NA	Intraocular gas known to persist for up to 4 weeks after injection.
Perfluoropropane, carbon octofluorine	NA	Intraocular gases known to persist for up to 6 weeks after injection.
Botulinum toxin	NA	Neurotoxin produced by Clostridium botulinum, which inhibits release of acetylcholine used for treatment of strabismus and blepharospasm.

Topical ophthalmologic agents have greater use than systemic agents in pediatric and adult populations, primarily because most of the side effects that would be consequential to systemic administration are diminished. Nevertheless, the excess from ocular application invariably enters the lacrimal system, reaching the nasopharyngeal mucosa where systemic absorption is greatly enhanced compared with that at the conjunctival sac. A single drop from a commercial eyedropper may have a volume ranging between 50 and 75 µL but maximal ocular bioavailability is reached by instillation of only 20 µL ( ). Digital pressure over the lacrimal duct for 5 minutes after instillation may reduce systemic absorption by 67% ( ). Keeping the eye gently closed for 5 minutes may afford similar benefit, yet both techniques are understandably difficult in the conscious and anxious child.

Cycloplegic and mydriatic agents

The agents used most commonly in the perioperative setting include cycloplegic and mydriatic agents. These agents are necessary for performing certain procedures, cycloplegic refraction, and fundoscopy. The cycloplegic agents act via parasympatholytic action to block the muscarinic receptors of the ciliary body, paralyze the ciliary muscles, and inhibit accommodation (the ability to change optical power to maintain focus). Outside of the perioperative period, cycloplegic agents are also used to decrease the discomfort of ciliary body spasm common to a variety of inflammatory conditions.

Cyclopentolate, a commonly used cycloplegic agent, has a peak effect within 20 to 45 minutes and residual effects that persist for as long as 36 hours ( ). Mild gastrointestinal discomfort and feeding intolerance are the most commonly encountered side effects, although more severe atropine-like toxicity with symptoms ranging from vomiting, ileus, hyperthermia, delirium, and grand mal seizures ( ; ) have also been reported.

Tropicamide is a belladonna alkaloid that is also used as a topical cycloplegic agent. Maximal cycloplegic effect takes place within 20 to 40 minutes, and residual effects may persist for 6 hours. Because tropicamide is less reliable than cyclopentolate, it is most often used in combination with cyclopentolate or phenylephrine.

Atropine and homatropine are extremely potent antiaccommodative agents that are rarely used for pediatric patients in the perioperative setting. These agents are more commonly used for intraocular inflammation and amblyopia therapy; they may also be used for prolonged mydriasis after cataract extraction to prevent the formation of synechiae. Common side effects include thirst, tachycardia, and hyperthermia, although more severe symptoms may result after overzealous administration ( ).

Mydriasis is usually produced as a secondary effect of the cycloplegic agents (by paralyzing the constrictors of the iris), yet additional mydriatic agents are often used to maximize peripheral and anterior retinal visualization. The mydriatic agents are sympathomimetic agents that mimic the effects of endogenous epinephrine and norepinephrine.

Ophthalmic phenylephrine (available in 2.5% and 10% concentrations) is commonly used for mydriasis and vasoconstriction during various procedures. Maximal effects are usually observed within 15 minutes, and residual effects may persist for 4 hours after administration. The generally accepted dosing limit for pediatric patients is 1 drop of the 2.5% solution in each eye per hour ( ). One drop (50 µL) of the 2.5% solution contains approximately 1.25 mg of phenylephrine. The potential for severe hypertension, pulmonary edema, cardiac arrhythmia, cardiac arrest, and subarachnoid hemorrhage with topical phenylephrine is well appreciated by surgeons and anesthesiologists alike. With careful application of the 2.5% solution, systemic effects are typically mild, well tolerated, and generally observed within 1 to 20 minutes after application ( ). Although one study demonstrated no significant difference in the mydriatic effects of cyclopentolate versus phenylephrine (both administered in combination with tropicamide), many ophthalmologists still rely on the medication either primarily or when additional dilation is needed after administration of other preparations ( ).

Glaucoma pharmacologic therapy

Unlike the management of adult glaucoma, the primary treatment for pediatric glaucoma is surgical when the condition is infantile or congenital glaucoma. Juvenile open-angle glaucoma is often initially medically treated. There are an expansive number of medications and combination products available, but none are formally approved for pediatric use. Convenient classifications for the glaucoma medications include the direct- and indirect-acting parasympathomimetics, sympathomimetics, beta antagonists, selective α ₂ agonists, carbonic anhydrase inhibitors, prostaglandin analogs, and hypertonic solutions.

Pilocarpine is a parasympathomimetic agent that produces miosis and a decrease in IOP that is thought to result from an increase in aqueous humor outflow. It is rarely used for temporary treatment before surgery in children but should be discontinued on the evening before surgery for adequate assessment of pressure ( ). At recommended dosages, side effects are thought to be rare but may include gastrointestinal disturbances and diaphoresis. More severe cardiovascular effects (e.g., hypotension, bradycardia, and atrioventricular block) are occasionally observed in the geriatric patient ( ).

The long-acting anticholinesterase drugs (echothiophate iodide and demecarium bromide) are uncommonly used in the pediatric patient. They are occasionally used in the adult refractory to other glaucoma therapy. These agents are of particular interest to the anesthesiologist because of their ability to profoundly inhibit the metabolism of succinylcholine, mivacurium, and the ester anesthetics for up to 6 weeks after discontinuation of therapy.

Topical epinephrine is occasionally used by ophthalmologists in the intraoperative setting prior to strabismus surgery to vasoconstrict the conjunctival vessels. It is known to potentiate dysrhythmias in the myocardium sensitized by the volatile agents. It is more of a historical note, but of all of the potent inhalation agents, halothane clearly has the greatest dysrhythmogenic potential, although one study has demonstrated that the pediatric heart may be more resistant to the interactions between halothane and exogenous epinephrine ( ; ). At equipotent concentrations, isoflurane has three times less dysrhythmogenic potential than halothane ( ). Desflurane and sevoflurane are thought to be similar to isoflurane in this regard ( ; ).

The beta-blocking agents timolol, levobunolol, and betaxolol act by decreasing the production of aqueous humor and are occasionally used postoperatively in children. The agents should not be used in the neonatal and infant populations in light of several reports of apnea with the use of timolol ( ; ). In older children and adults, the use of betaxolol, which is selective for the β ₁ -receptors, is associated with fewer complications involving the pulmonary system, although dyspnea and bronchospasm have been reported ( ). Lethargy, bradycardia, and heart block are possible with all of the topical beta-blocking agents ( ).

Apraclonidine and brimonidine are topical α ₂ agonists that decrease sympathetic tone and subsequently reduce aqueous humor production. Brimonidine, unlike apraclonidine, is capable of crossing the blood–brain barrier and should be used with great caution in young children. Bradycardia, hypotension, hypothermia, hypotonia, and apnea have all been reported with the use of brimonidine ( ; ).

Newer topical agents, including the prostaglandin analogs (latanoprost, bimatoprost, and travoprost) and the topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide), are generally very safe in the pediatric population but are believed to be less effective than they are in adults ( ). The topical carbonic anhydrase inhibitors, like systemic acetazolamide, are sulfonamide derivatives and should be avoided in the patient with sulfa sensitivity.

Miscellaneous ophthalmologic agents

Topical anesthetics, including cocaine, tetracaine, and proparacaine, are occasionally used by ophthalmologists in the perioperative setting. Compared with proparacaine 0.5% eyedrops, a single application of lidocaine 2% gel improves perioperative analgesia and reduces the incidence of PONV in elective pediatric strabismus surgery ( ). Cocaine is rarely used, but it is unique among the local anesthetics because of its vasoconstrictive properties. Both the surgeon and anesthesiologist should recognize the potential for serious cardiovascular and central nervous system effects. The accepted maximum dose is 3 mg/kg and 1.5 mg/kg in the presence of volatile anesthetics. One drop of the 4% formulation contains approximately 1.5 mg of cocaine ( ). The drug should not be used in patients with cardiovascular disease or in the presence of additional adrenergic-modifying medications, such as monoamine oxidase inhibitors or tricyclic antidepressants.

Intraocular gases, including sulfur hexafluoride, perfluoropropane, and carbon octofluorine, are poorly diffusible inert gases that may be injected during certain vitreoretinal procedures and in some anterior segment surgeries. When nitrous oxide is present during injection, the nitrous oxide equilibrates with these new gas spaces to increase the volume and pressure of the intraocular injection, potentially compromising retinal perfusion. Animal studies, case reports, and mathematical models have demonstrated the necessity of discontinuing nitrous oxide no less than 15 minutes before intraocular gas injection and avoiding subsequent use of nitrous oxide for at least 4 weeks after the use of sulfur hexafluoride and 6 weeks after the use of perfluoropropane or carbon octofluorine ( ; ; ).

Effects of various anesthetic agents on intraocular pressure

It is important to understand the ocular effects of the various anesthetic agents. An anesthetic plan should be chosen that provides optimal surgical conditions for intraocular procedures and minimizes the risk for morbidity in patients with preexisting intraocular hypertension and traumatic injury to the globe.

The central nervous system depressants (benzodiazepines, barbiturates, and opioids) commonly used by the anesthesiologist decrease IOP in both normal and glaucomatous eyes. The agents commonly used for preoperative anxiolysis in the pediatric population are associated with minor decreases in IOP that should not affect diagnostic measurements and likewise should not be relied on to attenuate the increase in IOP attributable to the use of succinylcholine and laryngoscopy. Two studies on the use of intravenous (IV) midazolam in adults demonstrate minimal effects on IOP ( ; ).

With the possible exception of ketamine, all of the IV induction agents are associated with a significant decrease in IOP. Thiopental and propofol reduced IOP by 40% and 53%, respectively, although in one study both agents were unable to completely attenuate increases that are secondary to succinylcholine and laryngoscopy ( ; ). Although etomidate decreases IOP ( ), etomidate-related myoclonus could be hazardous to the patient with traumatic injury and bothersome to the ophthalmologist. Early studies of the effects of ketamine uniformly demonstrated an increase in IOP, but subsequent studies in adults and children have demonstrated either insignificant changes or minor decreases in IOP ( ; ). There is no clear consensus regarding the effects of ketamine on IOP, although its association with blepharospasm and nystagmus makes other induction agents preferable for ophthalmologic surgery.

All of the volatile anesthetics are associated with a dose-dependent decrease in IOP. For this reason, it is important to allow a brief IOP check at induction as long as the airway is appropriately managed. Any concern about the airway must be communicated to the ophthalmic surgeon so that he or she is aware that an IOP measurement at induction may not be possible. Various postulated mechanisms for the reduction of the IOP with inhalational agents include a reduction in aqueous humor production with a concomitant increase in outflow, relaxation of the supporting musculature, and depression of the central nervous system control center for IOP ( ). As previously demonstrated with halothane, reliable measurements of IOP may be made for approximately 10 minutes after mask induction with sevoflurane ( ; ). Others maintain that it may be important to use ketamine as the induction anesthetic agent when accurate IOP measurement is necessary given that sevoflurane lowers IOP ( ; ).

For several decades, numerous investigators have evaluated the deleterious effects of succinylcholine on IOP and the various methods of attenuating these effects. The augmentation of IOP is thought to be mediated not only by tonic contractions of the extraocular muscles but also by dilation of the choroidal vasculature and relaxation of the orbital smooth muscle ( ). In a study of patients undergoing elective enucleation, the change in IOP after succinylcholine administration was the same in the normal eye as in the eye in which the extraocular muscles were detached; therefore it does not appear that extraocular muscle contraction significantly contributes to the increase in IOP after succinylcholine administration ( ). In adult patients with normal IOP, succinylcholine at doses between 1.5 and 2 mg/kg increased pressures by no more than 9 mm Hg, with peak effects demonstrated within 3 minutes after administration ( ). In patients who were not intubated, IOP was restored to baseline within 6 minutes, although other studies have demonstrated mild elevations that may persist for 30 minutes after succinylcholine administration. Whereas these effects of succinylcholine are significant in comparison with the effects of the nondepolarizing agents, they are clearly insignificant in comparison with the increase in IOP that is possible with laryngoscopy, coughing, and retching.

Numerous methods of blunting the rise in IOP secondary to succinylcholine and laryngoscopy have been evaluated, although none have demonstrated consistent or reliable efficacy. Early studies of pretreating patients with small doses of the nondepolarizing agents were promising but later refuted ( ; ). In two adult studies, the use of alfentanil was demonstrated to significantly attenuate the response to succinylcholine and intubation ( ; ). Another study comparing the effects of fentanyl and alfentanil demonstrated that although both agents were effective in attenuating the response to succinylcholine, fentanyl did not significantly attenuate the increase in IOP secondary to laryngoscopy ( ). Early studies concerning the benefit of lidocaine before succinylcholine were discouraging, but lidocaine had favorable effects on IOP during laryngoscopy and intubation in subsequent investigations ( ; ; ). Opioids and lidocaine may have the added benefit of facilitating gentle extubations after intraocular procedures and in patients with elevated IOP.

In adult patients, intravenous (IV) dexmedetomidine can attenuate the effects of succinylcholine and intubation on intraocular pressure ( ; ; ). In addition, IV dexmedetomidine attenuates IOP increases in adult patients undergoing robotic-assisted laparoscopic radical prostatectomy in the steep Trendelenburg position ( ). Intramuscular (IM) dexmedetomidine can also effectively reduce IOP in adults ( ). However, in the pediatric patient, Lili et al. reported no difference in IOP reduction between dexmedetomidine 0.5 mcg/kg and normal saline placebo groups during induction at similar anesthetic levels, suggesting that dexmedetomidine has no direct effect in IOP. They proposed that the reduction in IOP observed in adults with dexmedetomidine is attributable to decreases in blood pressure affecting IOP, an effect more profound in adults ( ). Other methods of controlling IOP with the use of succinylcholine and laryngoscopy in adults include premedication with sublingual nifedipine and oral clonidine ( ; ; ). However, these methods have not been evaluated in the pediatric population.

The role that succinylcholine plays in patients with open globe injuries has been reviewed by . In addition, airway management and the effects on IOP are further discussed in Chapter 40 : Anesthesia for Pediatric Trauma.

General anesthetic considerations

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