INJECTION of an inert gas into the vitreous of the eye is commonly performed as a treatment for retinal detachment, either as an office procedure (pneumatic retinopexy) or as part of a surgical repair. 1,2Nitrous oxide (N2O) has the potential to diffuse into closed gas-containing spaces, resulting in dramatic increases in pressure and/or volume. We report two cases of permanent postoperative blindness resulting from expansion of an intraocular gas bubble during administration of an N2O-containing anesthetic.

Case 1

A 37-yr-old man underwent a femoral-to-distal bypass graft of the left leg for a gangrenous left toe. Medical history included type 1 diabetes mellitus, hypertension, peripheral vascular disease, and end-stage renal disease. He had poor vision in both eyes, resulting from proliferative diabetic retinopathy and vitreous hemorrhage, and he had previously undergone laser treatment of both eyes, as well as two vitrectomies of the left eye (OS) and one vitrectomy of the right eye (OD), without placement of a gas bubble. Six weeks before vascular surgery, a limited superior retinal detachment developed in the patient and he underwent an office procedure in which perfluoropropane gas was exchanged for the fluid in the vitreous cavity OD, followed by laser treatment to the causative retinal tear. The patient had “hand motion” vision through the gas bubble, and an intraocular pressure (IOP) of 17 mmHg (normal, 8–22 mmHg) 2 weeks after placement. The gas bubble occupied approximately 60% of the vitreous volume and the retina was attached. During the preoperative evaluation, the anesthesiologist became aware of the patient's surgery history, but not the office visit or the gas placement. The vascular procedure was performed during general anesthesia with the patient in the supine position. Anesthesia was induced with propofol and maintained with 60% N2O in oxygen, isoflurane, and opioid. There were no periods of hypoxia or hypotension. The procedure lasted approximately 5 h. The patient had no complaints while awakening from anesthesia. Later that night, he reported tearing and loss of vision OD. An ophthalmology consultation was obtained. Fundoscopic examination revealed a pale, opaque retina with extreme narrowing of the arteries, an appearance typical of central retinal artery occlusion. There has been no recovery of light perception OD. Vision in OS is 20/50.

Case 2

A 19-yr-old woman underwent cadaveric pancreas and kidney transplantation. Medical history was significant for type 1 diabetes mellitus with retinopathy, hypertension, and hemodialysis-dependent end-stage renal disease. She underwent left eye surgery to treat proliferative diabetic retinopathy and a retinal tear at another institution 25 days prior to the transplant. No information about this procedure was available at the time of the transplantation surgery. Visual acuity was “hand motion” OS and “finger count” OD. She underwent the transplantation surgery during general anesthesia while in the supine position. Propofol was given for induction and anesthesia was maintained with isoflurane, N2O 60% in oxygen, and fentanyl. Total surgery time was 5 h. Systolic blood pressure was maintained around 140 mmHg throughout the procedure. Postoperatively, on the day of surgery, the patient reported pain OS. As she became more alert she noted no light perception OS. The ophthalmology service was consulted. The IOP OS was measured at 40 mmHg and the vitreous cavity was described as 100% filled with gas. The diagnosis of arterial occlusion to the retina resulting in loss of light perception was made. On postoperative day 1, IOP OS was 12 mmHg with 70% gas fill and the retina was gray. By postoperative day 4, the IOP OS was 5 mmHg and the vitreous cavity was 45% filled with gas. The optic nerve was erythematous and the retina was white. Discussion with the surgeon who performed the eye surgery revealed that sulfur hexafluoride gas had been injected into the vitreous cavity. Four months after the transplantation operation, visual acuity was “no light perception” OS and 20/400 OD. The patient continues to have progressive proliferative diabetic retinopathy in the remaining functional (right) eye.

The use of intraocular gas for the repair of retinal detachment has become common. 1,2Inert gases, such as perfluoropropane (C3F8) or sulfur hexafluoride (SF6), are mixed with air typically at concentrations that are nonexpansile and used to replace the fluid in the vitreous cavity to provide intravitreal tamponade. In addition to their use in the operating room, smaller amounts of expansile concentrations of gas (i.e. , 100% perfluoropropane) are introduced to repair simple retinal detachments in the clinic setting. Diffusion of N2O into intraocular gas or air has been demonstrated to dramatically increase IOP within 15–24 min of administration. 3–5Therefore, it is commonly avoided during retina surgery involving the placement of an intraocular gas bubble.

The loss of vision in both of these cases is believed to be the result of sustained high IOP from the expanding gas bubble, causing occlusion of the blood supply to the retina and optic nerve. Irreversible retinal damage has been shown after occlusion of the central retinal artery in numerous experimental models. 6–8Interruption of the retinal blood supply typically occurs when the IOP exceeds the systolic pressure in the retinal arterial vessels. 9,10The pressure in these vessels varies and is lower in patients with diabetes, older patients, and patients with atherosclerosis. 11–15The presence of type 1 diabetes mellitus and peripheral vascular disease probably placed these patients at a higher risk for this complication.

With the growing popularity of vitreous surgery and pneumatic retinopexy, these slowly reabsorbing gases reside in the vitreous cavity of many individuals. This underscores the need for careful history taking and a high index of suspicion in a patient with a history of retinal detachment or other medical condition (e.g. , diabetic retinopathy) that may have involved eye procedures. Even when the history of gas bubble placement is known, reabsorption time is not uniform or always predictable. Indeed, current published guidelines recommend avoidance of N2O for 10 days after sulfur hexafluoride injection, 5but the patient in case 2 experienced this complication 25 days after injection. Published reports show that perfluoropropane gas has a dwell time of 28 days, 16yet in patient 1 it occurred 41 days after injection. The gas bubble cannot be detected during physical examination, as it is not visible to the naked eye or with direct ophthalmoscopy. The presence of an intraocular bubble can only be reliably detected by indirect ophthalmoscopy.

For these reasons, we suggested to the manufacturers and distributors of these gases that a warning system be implemented. As a result of these discussions, Scott Specialty Gases, Inc. (Philadelphia, PA), the international distributor of medical-grade gases, in cooperation with USA distributors Alcon Laboratories, Inc. (Fort Worth, TX) and Infinitech, Inc. (St. Louis, MO), and the US Food and Drug Administration, has begun to provide hospital band-type warning bracelets to all facilities using these gases. The bracelets are placed on each patient who receives intraocular gas injection to alert other health professionals to the presence of the bubble and the need to avoid N2O administration. The bracelet is left on until the gas bubble reabsorbs. Also, we have added a “bubble in eye?” check box to our anesthesia preoperative evaluation forms as a reminder to seek this information before formulating the anesthetic plan for a patient.

Understanding the risk, as well as vigilance in history taking, will be necessary to avoid this devastating complication.

Benson WE, Chan P, Sharma S, Snyder WB, Bloome MA, Birch DG: Current popularity of pneumatic retinopexy. Retina 1999; 19: 238–41
Ai E, Gardner TW: Current patterns of intraocular gas use in North America. Arch Ophthalmol 1993; 111: 331–2
Smith RB, Carl B, Linn JG Jr, Nemoto E: Effect of nitrous oxide on air in vitreous. Am J Ophthalmol 1974; 78: 314–7
Stinson TW III, Donlon JV Jr: Interaction of intraocular air and sulfur hexafluoride with nitrous oxide, a computer simulation. A nesthesiology 1982; 56: 385–8
Wolf GL, Capuano C, Hartung J: Nitrous oxide increases intraocular pressure after intravitreal sulfur hexafluoride injection. A nesthesiology 1983; 59: 547–8
Hayreh SS, Kolder HE, Weingeist TA: Central retinal artery occlusion and retinal tolerance time. Ophthalmology 1980; 87: 75–8
Hayreh SS, Jonas JB: Optic disk and retinal nerve fiber layer damage after transient central retinal artery occlusion: An experimental study in rhesus monkeys. Am J Ophthalmol 2000; 129: 786–95
Zhu Y, Ohlemiller KK, McMahan BK, Gidday JM: Mouse models of retinal ischemic tolerance. Invest Ophthalmol Vis Sci 2002; 43: 1903–11
Attariwala R, Giebs CP, Glucksberg MR: The influence of elevated intraocular pressure on vascular pressures in the cat retina. Invest Ophthalmol Vis Sci 1994; 35: 1019–25
Kiel JW, van Heuven WA: Ocular perfusion pressure and choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci; 1995; 36: 579–85
Dallinger S, Findl O, Strenn K, Eichler HG, Wolzt M, Schmetterer L: Age dependence of choroidal blood flow. J Am Geriatr Soc 1998; 46: 484–7
Langham ME, Grebe R, Hopkins S, Marcus S, Sebag M: Choroidal blood flow in diabetic retinopathy. Exp Eye Res 1991; 52: 167–73
Groh MJ, Michelson G, Langhans MJ, Harazny J: Influence of age on retinal and optic nerve head blood circulation. Ophthalmology 1996; 103: 529–34
Recchia FM, Brown GC: Systemic disorders associated with retinal vascular occlusion. Curr Opin Ophthalmol 2000; 11: 462–7
Hayreh SS: Retinal and optic nerve head ischemic disorders and atherosclerosis: role of seratonin. Prog Retin Eye Res 1999; 18: 191–221
Lincoff H, Mardirossian J, Lincoff A, Liggett P, Iwamoto T, Jakobiec F: Intravitreal longevity of three perfluorocarbon gases. Arch Ophthalmol 1980; 98: 1610–11