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Case report

GB is a 57-year-old man who was referred to our neurosurgical clinic with bitemporal hemianopsia and panhypopituitarism associated with a sellar mass. Hormonal studies revealed that the tumor was biochemically inactive (null cell adenoma). The patient also has a 5-year history of orthostatic hypotension that has been controlled by midodrine at a dose of 10-mg by mouth 3 times daily. In light of the patient’s sellar mass with associated symptoms, an endoscopic transnasal transsphenoidal hypophysectomy was planned. On the morning of surgery, our patient took 10 mg of midodrine as well as 20 mg of prednisone.

We routinely administer local anesthesia with vasoconstrictor through the greater palatine foramen before endoscopic transnasal pituitary surgery. The procedure is performed using a 1.5-in 25-gauge needle bent at 70° to 80°. The needle is carefully inserted into the greater palatine foramen to a distance of 2.4 cm. The syringe plunger is withdrawn to assure the avoidance of intravascular injection. One and one half cubic centimeters of 1% lidocaine with 1:100°000 units of epinephrine are slowly and gently injected into the canal bilaterally. Successful injection provides vasoconstriction to the distribution of the sphenopalatine artery as well as anesthesia to the mucosa of the posterior nasal cavity, nasopharynx, cheek upper lip, maxillary sinus, and hard and soft palate .

Within 1 minute of the above-described injection, our patient sustained a rapid increase in blood pressure and pulse rate. Specifically, his blood pressure rose from 150/80 to 230/120 and his pulse increased from 65 to 130. This hyperdynamic response was quickly curtailed via administration of a combination of esmolol and nitroglycerin, and his blood pressure and heart rate returned to their preinjection levels within 2 minutes. To assess for any immediate, adverse neurologic sequelae, the patient’s neuromuscular blockade was reversed, and he was allowed to awaken completely. Examination did not reveal any apparent deficits. The planned hypophysectomy was then carried out without incident. No further topical or intramucosal vasoconstrictor was used during the surgery. No short- or long-term adverse effects from the hypertensive episode have arisen.

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Discussion

Midodrine is a selective α ₁ agonist that is approved by the Food and Drug Administration for the treatment of orthostatic hypotension . It is a prodrug that is converted to its pharmacologically active metabolite, desglymidodrine, via enzymatic hydrolysis. This agent causes an increase in blood pressure via arterial and venous vasoconstriction. Single doses range from 2.5 to 10 mg and affect an increase in blood pressure within 1 hour. The drug’s half-life is 2 to 3 hours, and its duration of action is 4 hours. Although midodrine is generally well tolerated by patients, a recent analysis revealed a high incidence of adverse reactions in patients being treated with it for orthostatic hypotension . The most common reported side effects are piloerection, pruritus, urinary retention, and supine hypertension . This latter side effect has led to the recommendation that patients not take the medication within 4 hours of bedtime and may have contributed to the observed hypertensive episode described here.

The goal of transoral greater palatine foramen injection before nasal surgery is to instill local anesthetic and vasoconstrictor into the pterygomaxillary fossa. This anatomical space contains the third division of the internal maxillary artery as well as the maxillary division of the trigeminal nerve and the sphenopalatine ganglion . The procedure was first described by Nevin and Puterbough in 1917 and has been modified and improved by several anatomical studies . Most recently, a cadaver-based study by Douglas and Wormald determined that the needle should be bent at 45° and inserted to a depth of 25 mm. Prevention of complications requires an understanding of the anatomy of this region as improper technique can result in ophthalmoplegia or blindness . Furthermore, aspiration of the syringe plunger before injection, which we perform in all cases, is critical to avoid intravascular injection. We have performed several hundred similar injections in patients not taking midodrine with no significant rise in blood pressure as monitored via arterial line.

Reports of cardiovascular complications from intranasal injection of vasoconstrictors have been described frequently in the medical literature even in patients who do not have underlying autonomic nervous system dysfunction . In 2004, Pasternak et al reported a significant hypertensive response in 58% of patients who received intranasal injection of lidocaine with epinephrine before transsphenoidal hypophysectomy. Furthermore, this report cites a 400% increase in circulating plasma epinephrine within minutes of injection of epinephrine-containing local anesthetic. Chelliah et al reported an incident of hypertensive crisis with associated myocardial infarction after a single intranasal injection of 1.5 mL injection of 1% lidocaine containing 10 μ g/mL epinephrine. The risk of hyperdynamic complications during surgery is known to be especially heightened by the presence of elevated glucocorticoid levels, such as is seen in patients with Cushing disease . Although our patient had a nonfunctioning adenoma, he was on prednisone for gout and did take 20 mg on the day of surgery.

Severe, transient hypertension has also been described during anesthesia induction, in the absence application of vasoactive local anesthesia, in patients taking midodrine for orthostatic hypotension . Furthermore, patients with primary autonomic dysfunction and orthostatic hypotension are known to be susceptible supine hypertension in absence of pharmacologic therapy. This problem is known to be exacerbated by midodrine therapy, which is associated with supine hypertension in 25% to 75% of patients . This effect can be severe and has been associated with associated intracranial hemorrhage .

The above analysis of the literature points to a multifactorial cause for our patient’s severe hypertensive episode. Specifically, the combination of intranasal epinephrine injection with the presence of midodrine and corticosteroid coupled with supine positioning in a patient with autonomic dysfunction likely led to the described reaction. Knowledge of this susceptibility in patients being treated with midodrine for orthostatic hypotension can prevent such a complication.