Preparing for Anaphylaxis from Fluorescein Angiography

3 02 2010

I was interviewed for an article that appeared in the January issue of Retinal Physician magazine. The article was titled, “Putting ‘Management’ Into Risk Management: Proactive policies for keeping patients safe.” My discussion regarding developing a plan for performing fluorescein angiography were rather comprehensive, so Retinal Physician turned it into a sidebar in the article. In my comments I mentioned that the protocol we developed for our office is available here at The Retina Blog. For some reason it seems to have disappeared. If you would like a copy, leave a comment (it will show your email address to me, but no one else can see it) and I’d be happy to send the protocol to you. I only ask that you let me know how useful you find the protocol, and if you have any suggestions for improvements.

Here is my discussion in the January 2010 issue of Retinal Physician:


The biggest risk we need to be prepared for in retina practices is anaphylaxis from fluorescein angiography. A publication this past summer showed the incidence of anaphylaxis is one per 350 fluoresceins.2 Because anaphylaxis can be life threatening, and because it is treatable, we must train our staff to recognize it — and our retina practices must be prepared to deal with it.

Anaphylaxis is a multisystem allergic reaction. The severity of the reaction is difficult to predict at its outset, and the internal medicine literature advocates treating it early with subcutaneous or intramuscular epinephrine (1:1000). Anaphylaxis can involve four major organ systems: respiratory, cardiovascular, gastrointestinal and cutaneous. Involvement of any two of these organ systems meets the definition of anaphylaxis. So if a patient has itching and shortness of breath, the internal medicine literature advocates treating with epinephrine. I think many of us are hesitant to give epinephrine in our practices because of the potential risks in our patients with diabetes and cardiac disease. But it’s certainly worth having epinephrine on hand. It’s also important to have a protocol in place.

In developing protocols for our practice, I consulted with other retina specialists to see what protocols they had in place. At hospital-based practices, the most common protocol was “call the code blue team.” Most private practices I spoke to don’t have written protocols. In developing ours, I sought the advice of my colleagues in internal medicine, emergency medicine and anesthesia. Among these specialties, they advocated a wide range of reasonable approaches. If you have easy access to a 911 team, then your protocol can be minimal — administer diphenhydramine, maybe epinephrine, and monitor blood pressure. If, however, you want to be more complete, because of a slower anticipated response time, your protocol could include administering oxygen or IV fluids, monitoring oxygen saturation and a cardiac tracing, and having available an airway, bag and an automatic external defibrillator.

Our protocol is primarily a checklist that includes several sections: preparation, which includes checking the blood pressure and pulse, reviewing drug allergies, pregnancy, and any history of prior cardiac or respiratory problems. Most of these data are already on the chart, so this portion of the checklist is a sort of a “time out” to review things before injecting the fluorescein.

The second portion of the checklist addresses things that must be available prior to injecting: Personnel —which is an MD in the office; Equipment — which, in our case, is a cardiac monitor, and bag and mask; Supplies — such as IV fluid, needle, tape and gauze; Drugs — we stock oral and IV diphenhydramine, and IM/SQ epinephrine (1:1000); and Paperwork — the consent form, the symptoms checklist, and treatment flowsheets.

The protocol in our practice is symptom-based. For example, if there is nausea or vomiting, the protocol directs staff to provide an emesis basin, support, and monitor the patient for 30 minutes. In the event of mild hives or itching, the protocol calls for notification of the MD, the administration of oral diphenhydramine 25-50 mg, and monitoring until symptoms improve. For more severe hives or itching, we administer the drug IV.

In the event of the onset of respiratory symptoms, our protocol calls for us to record oxygen saturation and blood pressure, to call 911, to prepare the epinephrine for possible administration, and to get the doctor in the emergency room on the phone for guidance while awaiting arrival of the emergency team. Our entire protocol is available online at

The truth is that severe symptoms are rare, and fortunately, death from fluorescein angiography is reported to be only 1/220,000. But it is prudent to be prepared to deal with the more severe symptoms in the unlikely event they arise.

In terms of training, I think we physicians have to periodically review the management of anaphylaxis, and an excellent review is available in the article, “Office Approach to Anaphylaxis: Sooner Better than Later” by Stephen F. Kemp, which appeared in the Amercian Journal of Medicine (2007) 120, 664-668.

I do think it’s reasonable for nonphysicians to administer fluorescein, under the supervision of a physician.* In our case, it means that they have shown their ability to administer FA successfully 10 times under direct physician observation. After that, a physician must be present in the office and available to deal with any emergencies during administration. In our office, all staff (including doctors) maintain current CPR certification.

* OMIC warns that allowing unlicensed staff to inject may be illegal. See their risk management recommendations on FAs.

Bilateral same-day intravitreal injections? Yes!

8 01 2010

One of the growing issues in treating age-related macular degeneration (AMD) is to reduce the burden of treatment for the patients, many of whom are elderly, and may require injections of VEGF inhibitors every 4-8 weeks. A long-standing tradition in ophthalmology has been to avoid bilateral same-day surgical intervention. The rationale has been that if you operate on two eyes on the same day, any infection that develops in one eye may spread to the other eye, and that if there is any contamination of instruments or compounds used during the surgery, operating on both eyes on the same day increases the likelihood that both eyes will be adversely affected.

Intravitreal injections, which have become standard of care for treatment of AMD are fairly innocuous in terms of surgical insult. The “wound” is a 31 gauge needle entry site. Nevertheless, endophthalmitis may develop. For example, in the VISION study of intravitreal pegaptanib, the incidence of endophthalmitis was 0.16%. In the MARINA study of intravitreal ranibizumab, it was 0.05%. And in the ANCHOR study of ranibizumab, it was 0.05% (3 cases our of 5,921 injections). A study by Pilli et all reported an incidence of 0.029% (3 cases in 10,254 injections). These incidences were for unilateral injections.

So, is there an increased risk for bilateral same-day injections? Lima et al (Yannuzzi’s group) out of New York published their retrospective analysis of bilateral same-day intravitreal injections of VEGF inhibitors in the October 2009 issue of Retina. They report that of 1,534 bilateral injections (3,068 injections total), the incidence of culture-proven endophthalmitis was 0.065%, and the incidence of acute intraocular inflmaation was 0.033%. None of those cases were bilateral. There were no cases of retinal breaks. They conclude that it appears that there is no increased risk for same-day bilateral injections of VEGF inhibitors, as the complication rates are similar.

It’s noteworthy that all patients in their study were done in the office, and received surface disinfection with 5% providone-iodine solution, followed by 2 days of either polytrim or ofloxacin qid.

The study is very useful and gives comfort to those of us considering bilateral same-day injections. In any disease process where the incidence of an occurence is very low, large numbers of patients are needed to determine whether or not there is a difference in incidence between groups, and so, it is fair to say that there is no obvious increase in the risk of complications from bilateral VEGF inhibitor injections, while recognizing the limitation of the comparison.

Improving intravitreal injections

25 10 2009

Have you ever noticed that when you give an intravitreal injection of bevacizumab, or some other drug, a bleb seems to rise on the conjunctiva immediately after injection?  Presumably, that bleb is reflux of the drug (or vitreous).  One way to avoid this, is to simply start the injection at a 30 degree angle to the tangent to the globe.  Just as the needle enters the sclera, turn the needle so it is going straight in (90 degrees to the tangent), and then enter the vitreous.  This effectively creates a “bi-planar” path of the needle, and reduces reflux of the drug.

The technique is described briefly in the September 2009 issue of Retina in an article by Pascal Knecht et al. out of Switzerland.  In their study, they compared the straight ahead injection to the “bi-planar” injection (which they call “tunneled”, but they’re both tunneled, aren’t they?).  They looked at three parameters after injection 0.05 mL of bevacizumab: rise in intraocular pressure, amount of vitreous reflux, and patient discomfort.  The IOP increased more in the tunnelled group (avg 35 mmHg) vs. the straight group (avg 30 mmHg), but after 5 minutes there was no IOP difference between the two groups.  After 15 minutes, both groups were less than 30 mmHg.  Good news on that front.

The amount of vitreous reflux was measured by documenting the width of the broadest conjunctival elevation at the injection site, i.e. the width of the bleb.  They were graded as either 1mm, 2mm, and >2mm.  Not surprisingly, the straight technique had more reflux.  20/30 patients in the straight group had reflux, whereas only 8/30 in the tunneled group had reflux.  The amount of reflux was also more in the straight group.

Finally, there was no difference in pain between the two groups.

Since reading this article, I’ve started the bi-planar “tunneled” technique.  The key is to turn the needle from 30 degrees to 90 degrees while the needle is only partially through the sclera.  I’ve also found it helps prevent reflux to withdraw the needle slowly after the injection, and I actually turn the needle back to the 30 degree angle as the tip emerges from the globe.