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.

Risk of Stroke with Lucentis vs. Avastin

25 10 2009

In the February 2009 issue of Ophthalmology, a meta-analysis was reported in a letter to the editor pointing out some risks associated with intravitreal injection of ranibizumab (Lucentis). The letter looked at pooled data from the MARINA, ANCHOR and FOCUS studies which were done to determine effectiveness and adverse effects of Lucentis. The authors of the letter point out that when pooling all the data, the ranibizumab group had a 2.2% incidence of stroke, whereas the control group had a 0.7% incidence of stroke. They conclude that the risk of stroke rises as a result of ranibizumab treatment. When they look at the incidence of myocaridal infarction (MI), the ranibizumab group had a 1.9% incidence whereas the control group had a 3.0% incidence. They did not “conclude” that intravitreal injection was protective for MI, but the incidence is lower in the group receiving the drug vs. the control group.

Since the letter was published, there has been some discussion regarding the implications of this meta-analysis for those of us using Avastin. At the current time the feeling is that this data cannot be extrapolated to Avastin, in part because Avastin is a larger molecule (the entire globulin, vs. the immune arms as with ranibizumab). This molecular characteristic is felt to result in less egress of Avastin into the systemic circulation, and it is to this characteristic that the longer-acting effect of Avastin has been attributed. There is currently an NIH sponsored head-to-head clinical trial comparing Lucentis and Avastin underway. The results are due in 2012. The study is ongoing, and the fact that it has not been stopped is some solace to those of us who prefer Avastin that the study has not to date shown that Avastin is either hugely inferior or has significantly higher side-effects that Lucentis.