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CRITICAL CARE AND TRAUMA

Blindness in the Intensive Care Unit: Possible Role for Vasopressors?

Lorri A. Lee, MD^*, Avery B. Nathens, MD^,, Bryan S. Sires, MD, PhD, Megan K. McMurray, PharmD^||, and Arthur M. Lam, MD, FRCPC^*,¶

Departments of *Anesthesiology, Surgery, Critical Care, Ophthalmology, ||Pharmacy, and ¶Neurological Surgery, University of Washington, Seattle, Washington

Address correspondence and reprint requests to Lorri A. Lee, MD, Harborview Medical Center, Department of Anesthesiology, Box 359724, 325 Ninth Ave., Seattle, WA 98104. Address e-mail to lorlee{at}u.washington.edu

	Abstract

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Blindness caused by ischemic optic neuropathy in the hospital setting occurs perioperatively and in critically ill patients, but its etiology remains ill defined. We describe four critically ill patients who developed blindness within 1 mo of one another. Three cases occurred outside of the operative arena. Potential risk factors for the development of ischemic optic neuropathy, such as use of vasopressors, venous congestion, and hypotension, are described.

IMPLICATIONS: Four cases of blindness in critically ill patients are described, three of which occurred outside the operative arena. Venous congestion and hypotension are among the potential risk factors for the development of ischemic optic neuropathy. The role of vasopressors remains speculative but should be considered during treatment of critically ill patients.

	Introduction

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Ischemic optic neuropathy (ION) is the most common diagnosis for perioperative visual loss (1,2). Most reports have focused on patient risk factors and intraoperative events, particularly in association with spine surgery in the prone position. However, many of these patients are critically ill perioperatively and incur other complications, including renal failure, cardiac and pulmonary dysfunction, and brain damage. Although blindness is a rare complication in the intensive care unit (ICU), we describe a series of four patients admitted within 1 mo of one another who developed blindness as a result of ION (three patients) or combined traumatic optic neuropathy (TON) and ION (one patient) (3). Three of the four patients had had visual deficits before any operative procedures, and none of the patients was ever positioned prone. Risk factors for the development of ION in these patients are discussed.

	Case Reports

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Case 1
A 58-yr-old man with a history of insulin-dependent diabetes and myocardial infarction was admitted with the diagnosis of acute pancreatitis complicated by sepsis and diabetic ketoacidosis (Table 1). The patient had been vomiting for several days at home and was tracheally intubated in the field for airway protection because of increasing somnolence. He was severely hypovolemic, with an admission systolic blood pressure (SBP) of 68 mm Hg, arterial pH of 6.9, and glucose of 824 g/dL. Thirty liters of crystalloid and blood products was administered during the first 18 h of admission for hypotension, low urine output, and diabetic ketoacidosis until adequate filling pressures were obtained (central venous pressure [CVP], 10–14 mm Hg). He developed acute tubular necrosis (ATN) requiring continuous veno-veno hemodialysis. Within 24 h, he developed adult respiratory distress syndrome (ARDS), as defined by standard criteria, with a PaO₂ between 51 and 65 mm Hg for 14 h. This necessitated positive end-expiratory pressure (PEEP) of 25 mm Hg and an inspired oxygen fraction (FIO₂) of 1.0 (4). The etiology of the ARDS was assumed to be aspiration pneumonia with Group B ß-hemolytic streptococci in combination with severe acute pancreatitis. CVP was 16–22 mm Hg with high levels of PEEP, and hematocrit ranged from 28% to 38%. Because of an initial systemic vascular resistance (SVR) of 407 dynes · cm · s^–5 with systemic hypotension and no further improvement in mean arterial blood pressure (MAP) with fluid challenge, MAP and cardiac output were optimized with vasopressin infusion for >4 days in combination with norepinephrine infusion for 2.5 days.

Case 2
A 50-yr-old male pedestrian was hit by a car and sustained a right-sided LeForte III fracture without optic canal involvement, a nonoperative right-sided subdural hematoma, and an L2 spine fracture. A cervical collar and an intracranial pressure (ICP) recording device were placed in the emergency room. On arrival to the ICU, he presented in vasodilatory shock of unknown etiology, with a MAP of 46 to 62 mm Hg for the initial 3 h, an SVR of 250 dynes · cm · s^–5, a cardiac index of 6 L · min^–1 · m^–2, and an arterial pH of 7.2. No operative internal injuries were found, and he had a relatively normal transesophageal echocardiogram. He received 19 L of crystalloid and 3 L of blood products in the first 24 h, along with a vasopressin infusion for 4 days in combination with norepinephrine infusion for 1 day, for treatment of his vasodilatory shock. The target MAP was 70 mm Hg because of his associated brain injury. On hospital Day 2, he developed abdominal compartment syndrome secondary to reperfusion injury of the bowel and mesentery. Consequently, CVP increased to 41 mm Hg and ICP increased to 31 mm Hg, and the patient underwent a decompressive laparotomy the next day for inability to ventilate and oxygenate. PaO₂ was <60 mm Hg during the initial 24 h, necessitating a PEEP of 25 mm Hg and an FIO₂ of 1.0, and hematocrit ranged from 23% to 32%.

Pupillary examination in the emergency room had demonstrated a nonreactive right pupil and a sluggishly reactive left pupil. On the second hospital day, when the patient’s abdominal compartment syndrome was diagnosed and ICP and CVP were increased, his pupils were nonreactive bilaterally. Intraocular pressures (IOPs) were 35 to 38 mm Hg, with severe periorbital edema. Visual evoked potentials were absent bilaterally on the seventh hospital day, with normal IOPs and funduscopic examination. Two weeks later, bilateral global optic nerve pallor was present. The patient was diagnosed with TON of the right eye because of his associated right LeForte III fracture and absent light reflex in the emergency room (5). The left eye was diagnosed as having posterior ION (PION) or TON.

Case 3
A 53-yr-old male pedestrian was hit by a car and sustained lower extremity and pelvic fractures and flail chest with acute lung injury and hemothorax. No facial fractures were identified. The initial arterial pH was 7.26, and he required 21 L of crystalloid and 3 L of blood products in the first 12 h for intermittent hypotension responsive to volume and low hematocrit. On the second hospital day, he developed vasodilatory shock of unknown etiology with an SBP of 68 mm Hg, an SVR of 384 dynes · cm · s^–5, and a CVP of 26 mm Hg while on 25 mm Hg PEEP. He was placed on norepinephrine infusion followed by vasopressin infusion for >24 h. SBP was <90 mm Hg for approximately 2 h. PaO₂ ranged from 56 to 66 mm Hg during the initial 8 h, and he was ventilated with a PEEP of 25 mm Hg and an FIO₂ of 1.0. CVP was 22–26 mm Hg for 3–4 days after admission while he was on high levels of PEEP.

An ophthalmologic examination was performed on day 27 for a complaint of no vision in his right eye. His pupils were initially reactive to light bilaterally, but the right eye was now noted to have an afferent pupillary defect and no light perception. IOPs were normal. Funduscopic examination revealed a normal left eye but global optic nerve pallor in the right eye, consistent with ION.

Case 4
A 50-yr-old woman with hypertension who was status postthymectomy for myasthenia gravis arrived in the emergency room hypoxemic and hypotensive secondary to perforated sigmoid diverticulitis with sepsis. She had a brief (<5-min) period of pulseless electrical activity requiring cardiopulmonary resuscitation and was then emergently taken for exploratory laparotomy. She required large volume administration and multiple vasopressor infusions (added sequentially) during surgery, including vasopressin, norepinephrine, epinephrine, and phenylephrine. MAP ranged from 38 to 49 mm Hg perioperatively for a total of 3.5 h. Initial arterial pH was 7.3. Postoperative pulmonary artery catheter placement demonstrated a cardiac index of 2.1–2.6 L · min^–1 · m^–2, a CVP of 26 mm Hg (on 25 mm Hg PEEP), and an SVR of 1000 to 1200 dynes · cm · s^–5. Dobutamine was added after surgery for >24 h to improve inotropy, and she was weaned from vasopressin, norepinephrine, and epinephrine infusions over the next 48 h guided by SVR and cardiac index. Because of the need for perioperative volume resuscitation and bicarbonate infusion for acidosis, she received 24 L of crystalloid and 3 L of blood products during the first 24 h. She developed ATN with a subsequent increase of her CVP from 25 to 40 mm Hg and required emergent continuous veno-veno hemodialysis the night of admission. PaO₂ was <60 mm Hg for the first 4–5 h after admission, requiring a PEEP of 25 mm Hg and an FIO₂ of 1.0. Her troponin levels peaked at 29 ng/mL. A head computed tomography scan performed on the ninth day for decreased mental status demonstrated two small strokes in the left frontal hemisphere. No occipital infarcts were seen.

Ophthalmological examination on day 34 for a complaint of blindness revealed no light perception bilaterally, normal IOPs, and a normal fundus. Global optic nerve pallor was present bilaterally by the 42nd hospital day, consistent with ION.

	Discussion

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Although blindness is an uncommon complication of critical illness, we identified four patients within a one-month period in the same hospital who developed blindness after vasodilatory shock/sepsis, ARDS requiring high levels of PEEP, and hypotension requiring massive fluid resuscitation and multiple vasopressors. Three patients were diagnosed with ION, and one patient was diagnosed with TON in one eye and PION or TON in the other eye. Three of the four patients had documented visual deficits or abnormalities before any operations. No patient was positioned prone. Factors suggested to be associated with perioperative ION include hypotension, anemia, venous congestion, prone position, periorbital edema, large blood loss, use of vasopressors, and preexisting vasoocclusive disease (2,6). The previous report of nine ICU patients with anterior ION diagnosed over seven years did not describe the use of vasopressors, and at least eight of these nine patients had surgical procedures before their diagnosis of vision loss (3).

The effect of vasopressors on optic nerve blood flow has not been well studied because there is currently no satisfactory method of directly measuring posterior optic nerve blood flow in humans. Isolated and perfused simian ophthalmic and ciliary arteries demonstrated marked vasoconstriction with injection of norepinephrine, phenylephrine, and serotonin (7). Inadvertent injection of epinephrine into the human ophthalmic artery has resulted in blindness caused by either retinal artery occlusion or ION (8). Epinephrine is postulated to cause severe vasospasm of the ocular vessels. Epinephrine and amrinone administration have been associated with anterior ION after cardiopulmonary bypass (6). In addition, many studies have demonstrated defective vasodilation and increased responsiveness to vasoconstrictors in atherosclerotic vessels (9–11).

The four patients in this report all received two or more vasoconstrictors to support their MAP. Norepinephrine and vasopressin were administered simultaneously in three of the four patients on the basis of previous studies that demonstrated improved hemodynamic profiles and gut perfusion with this vasopressor combination compared with norepinephrine alone in patients in vasodilatory shock (12). The duration of vasopressin infusion ranged from 27.5 to 100.5 hours at doses of 0.04–0.09 U/min. Norepinephrine infusion ranged from 2.5 to 61 hours at doses of 0.02–0.55 µg · kg^–1 · min^–1. Additionally, two patients received dobutamine, one patient received epinephrine, and one patient received dopamine simultaneously with vasopressin and norepinephrine.

As is our usual ICU practice, pulmonary artery catheters were eventually used in all four cases for hypotension of unknown or mixed etiology. Volume administration was guided by filling pressures (when available) and/or response to fluid challenge. Vasopressors are added in our institution when patients exhibit hypotension with low SVR and when filling pressures have been optimized. Inotropes are initiated for hypotension with low cardiac output and adequate filling pressures.

Venous congestion has been implicated as a causative factor for perioperative PION because it is most frequently observed after prone spine surgery or bilateral radical neck dissections in which both internal jugular veins are ligated. The prone position is known to cause an increase of CVP and IOP, presumably from compression of the inferior vena cava and increased intrathoracic pressure (13,14). Ligation of bilateral internal jugular veins reduces venous outflow from the head and can increase ICP (15). The posterior optic nerve is supplied by small pial vessels that are easily compressed. PION has been postulated to result from high venous back-pressure and edema formation in the presence of low inflow from systemic hypotension. Abdominal compartment syndrome, as seen in our Case 2, can significantly increase CVP and ICP, and cervical collars are known to increase ICP (16,17). Moreover, ATN and high levels of PEEP in Cases 1 and 4 further increased CVP.

Anatomic variation in the vascular watershed zones (18) and lack of autoregulation of blood flow (19) in the optic nerve head have been demonstrated in healthy subjects. Therefore, some patients may not be able to maintain constant perfusion to the optic nerve in the presence of hypotension and/or venous congestion.

In summary, all four patients had multiple conditions in common that may have predisposed them to the development of ION. Hypotension, venous congestion, high levels of PEEP, hypoxemia, large-volume fluid resuscitation, and prolonged infusions of multiple vasopressors were present in each patient concurrently. In addition, they all had documented, or significant risk factors for, atherosclerosis (Table 1). The relative contribution of each of these factors is speculative, and management of critically ill patients is frequently controversial. Moreover, it is difficult to make recommendations for these patients, without risking their death, regarding alternative therapy to avoid the devastating visual outcome. As ICU therapy advances, the cost of improved survival may be increased morbidity and end-organ sequelae. The optic nerves may be as susceptible to ischemia as the heart, brain, and kidneys. Further research on factors that affect the blood supply to the optic nerve is needed before definitive recommendations can be made. Until that information becomes available, heightened awareness of the potential for ION in critically ill patients outside of the operative setting is warranted.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Lee, L. A. Articles by Lam, A. M. Search for Related Content PubMed PubMed Citation Articles by Lee, L. A. Articles by Lam, A. M. Related Collections Critical Care Complications