Ophthalmic Safety Alert – Do not use nitrous oxide when there is gas in an operated eye

  • 18 Dec 2018
  • RCOphth

Intraocular air or gas is often used as a tamponade agent at the end of vitrectomy surgery to secure the retina. The two most common indications are retinal detachment and macular hole surgery. Intraocular gas is also being used increasingly in endothelial keratoplasties (lamellar corneal grafts) initially during the primary procedure or for “rebubbling” dislocated grafts. The intraocular gas only remains in the eye for a short time and is then resorbed but, whilst the gas is present in the eye, there are certain precautions that need to be taken to avoid harm to the eye and vision.

These tamponade agents have different properties and characteristics1 and the choice of tamponade depends on the indication of use and the duration of tamponade required.

Properties of commonly used gas tamponades in vitrectomy surgery

Gas tamponades Chemical formula 100% gas expansivity 100% maximum expansion Time gas remains in eye Isoexpansile concentration
Air NA NA NA 5-7 days NA
Sulfur hexafluoride SF6 2X 1-2 days 2 weeks 20%
Perfluoroethane C2F6 3X 1-3 days 4-5 weeks 16%
Perfluoropropane C3F8 4X 3-4 days 8 weeks 14%

Intraocular gas and interaction with nitrous oxide
Retinal surgeons are well aware of the risks of expansion of these intraocular gases during air flight or at high altitude. A less appreciated danger is with the use of nitrous oxide, sometimes used in general anaesthesia and also found in Entonox and Equanox (‘gas and air’, 50% nitrous oxide and 50% oxygen), used as a short term inhaled analgesic agent in conscious patients for pain relief in trauma, painful procedures and during labour. Nitrous oxide can also be used as a drug of abuse.

Nitrous oxide has a high diffusion and solubility co-efficient, causing it to diffuse down its concentration gradient much quicker than other gases such as nitrogen, oxygen and carbon dioxide. Nitrous oxide diffuses into closed spaces with resultant increase in pressure. In an eye with intraocular gas, the net effect is an expansion of the gas bubble that leads to rapid increase in intraocular pressure with subsequent risk of reduced perfusion to the central retinal artery, causing retinal ischaemia and infarction.

There have been several case reports on the use of nitrous oxide in the presence of intraocular gas after vitreoretinal surgery with severe loss of vision due to central retinal artery occlusion.2-6 There have also been some cases identified via national incident reporting systems. Nitrous oxide leaves the bloodstream and vitreous cavity quickly once inhalation is terminated,7 restoring the position of the lens-iris diaphragm and reperfusion of the central artery can happen. However, irreparable damage to the retina is known to occur after 100 minutes of ischaemia.7 The extent of damage to the eye may therefore be dependent on the duration of general anaesthesia / use of Entonox and the size of intraocular gas bubble at that time.

There is a theoretical risk of harm (raised intraocular pressure or hypoxic iris) in anterior chamber gas bubbles during keratoplasty in the same circumstances, that is flying, high altitude or nitrous oxide use. It is currently unclear whether this represents a significant risk, as there is little published, but some corneal surgeons are warning their patients not to fly postoperatively.

Advice and recommendations

  1. Ophthalmic units should warn patients about the risks of flying, general anaesthetic, gas analgesia and the use of nitrous oxide / Entonox / Equanox, recreational abuse of nitrous oxide following vitrectomy or keratoplasty surgery in the presence of intraocular gas. Patients need to understand specifically that nitrous oxide gas may be used by for pain relief by ambulance, maternity or A&E staff. An information leaflet should be given before and/or after surgery alerting them of these risks. The responsible unit can refer to patient information leaflet on intraocular gas approved by the members of the British and Eire Association of Vitreoretinal Surgeons (BEAVRS). We are exploring the potential to provide the key information from the leaflet as a card or bracelet for patients to hand to healthcare staff and would update via Royal College newsletters when these became available; in the interim patients should be encouraged to carry the patient information leaflet with them and show it to healthcare staff wherever they need treatment.
  2. Ophthalmic surgeons should ensure each patient’s medical records (paper and/or electronic) carry a clear warning of the need to avoid Entonox / Equanox / anaesthesia until the appropriate post-procedure date, displayed in an area of the electronic record/paper notes that would be picked up by other specialities if the patient presented for emergency or elective treatment (including on any patient-held records such as maternity notes).

Quality and Safety Group
December 2018


1. Vaziri K, Schwartz SG, Kishor KS, et al. Tamponade in the surgical management ofretinal detachment. Clin Ophthalmol 2016;10:471-6. doi: 10.2147/OPTH.S98529 [published Online First: 2016/03/16]
2. Lee EJ. Use of nitrous oxide causing severe visual loss 37 days after retinal surgery. Br J Anaesth 2004;93(3):464-6. doi: 10.1093/bja/aeh213 [published Online First: 2004/06/25]
3. Seaberg RR, Freeman WR, Goldbaum MH, et al. Permanent postoperative vision loss associated with expansion of intraocular gas in the presence of a nitrous oxide-containing anesthetic. Anesthesiology 2002;97(5):1309-10.
4. Lockwood AJ, Yang YF. Nitrous oxide inhalation anaesthesia in the presence of intraocular gas can cause irreversible blindness. Br Dent J 2008;204(5):247-8. doi: 10.1038/bdj.2008.158
5. Yang YF, Herbert L, Rüschen H, et al. Nitrous oxide anaesthesia in the presence of intraocular gas can cause irreversible blindness. BMJ 2002;325(7363):532-3.
6. Fuller D, Lewis ML. Letter: Nitrous oxide anesthesia with gas in the vitreous cavity. Am J Ophthalmol 1975;80(4):778-9.
7. Lincoff A, Lincoff H, Solorzano C, et al. Selection of xenon gas for rapidly disappearing retinal tamponade. Arch Ophthalmol 1982;100(6):996-7.