Archives of Academic Emergency Medicine. 2019; 7 (1): e18 CA S E RE P O RT Pulmonary Edema Following Intrathecal Fluorescein In- jection; a Case Report Faranak Behnaz1∗, Masih Ebrahimy Dehkordy1, Hamidreza Azizi Faresani1, Mohammadreza Shahmohammadi2 1. Anesthesiology Department, Shohadaye Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2. Functional Neurosurgery Research Center, Shohadaye Tajrish Neurosurgical Comprehensive Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Received: November 2018; Accepted: December 2018; Published online: 12 February 2019 Abstract: Intrathecal Fluorescein has been used widely for detection of cerebrospinal fluid (CSF) leakage. After adminis- tration of fluorescein many serious complications may happen. Pulmonary edema is one of the most serious complications that require emergency responses. In this study, we report a complicated case of pulmonary edema following Intrathecal fluorescein injection. Keywords: Pulmonary edema; injections, spinal; fluorescein; emergency treatment; complications; cerebrospinal fluid leak Cite this article as: Behnaz F, Ebrahimy Dehkordy M, Azizi Faresani H, Shahmohammadi M. Pulmonary Edema Following Intrathecal Fluo- rescein Injection; a Case Report. Arch Acad Emerg Med. 2019; 7 (1): e18. 1. Introduction Intrathecal injection of a sodium fluorescein solution follow- ing a thorough endoscopic examination has been used to identify the site of cerebrospinal fluid (CSF) leakage (1, 2). Sodium fluorescein has a relatively low molecular weight and is a highly water-soluble compound. It is well tolerated by most patients, but its intrathecal injection is an invasive pro- cedure with an associated risk of complications. Compli- cation occurs in 5-10% of patients and ranges from mild to severe (3, 4). Severe reactions are not common, but laryn- geal edema, pulmonary edema, anaphylaxis, status epilepti- cus, myocardial infarction and cardiac arrest have been re- ported as some of its complications (5-7). Non-allergic his- tamine release in the absence of antigen-antibody reaction (anaphylactoid reactions); vasovagal phenomenon resulting in bradycardia, arterial hypotension and reduced cardio- vascular perfusion; immediate hypersensitivity reaction to the drug (anaphylactic reactions); anxiety-related medullary sympathetic discharge, eliciting tachycardia and myocardial stress; and direct vasospastic toxic effect of intravenous in- jection are among the proposed mechanisms for occurrence of complications (8-10). In this study, we report a compli- ∗Corresponding Author: Faranak Behnaz; Anesthesiology Department, Shohadaye Tajrish Hospital, Shardari Av, Tajrish Sq, Tehran, Iran. Zip code; 1989934148, Email: faranak.behnaz@gmail.com Tel: 00982122741174 cated case of pulmonary edema following intrathecal fluo- rescein injection. 2. Case presentation: A 33-year-old man presented with 8-month history of in- termittent cerebrospinal fluid (CSF) leakage from his nos- tril following removal of fringe body from his orbital cav- ity. In medical history, the patient had eye trauma, mild asthma, and was under treatment of glaucoma with Timolol eye drop. He was admitted to the operating room for trans- sphenoid endoscopic surgery. His preoperative blood pres- sure measured via noninvasive method was 135/80 mmHg and he had a pulse rate of 90/minute with normal respira- tory rate and O2 Saturation of 100% with oxygen. Labora- tory findings showed fasting blood sugar (FBS): 93 mg/dl, blood urea nitrogen (BUN): 20 mg/dl, creatinine: 0.8 mg/dl, sodium: 138 mEq/L, hemoglobin: 13.3 g/dl, platelet: 260000 /microliter, and international normalized ratio (INR): 1. His imaging result was normal, and normal cardiovascular risk for operation was reported in pre-operation cardiology con- sultation. He underwent cardiac and invasive blood pres- sure (IBP) monitoring, pulse oximetry, capnometry, and in- take/output checking. Anesthesia was induced via Fentanyl (200 micg), Midazolam (2 mg), Lidocaine (80 mg), Propofol (200 mg), Cisatracuriom (18 mg), and then orotracheal in- tubation was done. After positioning of the patient, 0.5 cc of fluorescein 5% was mixed with 10 cc of the patient’s CSF This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem F. Behnaz et al. 2 Figure 1: Changes observed 10 minutes after intrathecal fluorescein injection. and then re-injected via a lumbar puncture at the level of L4-L5 spinal column. After 10 minutes, the patient’s blood pressure dropped unexpectedly (IBP: 87/50 mmHg), and his pulse rate rose to 124/minutes and O2 saturation dropped to 85%. Shortly after this event, some pink foamy secretions ap- peared in the transparent circuiting tube of the anesthesia machine and suction bottle cavity and urine color changed to shiny green (figure 1). Patient underwent immediate sup- portive vital managements including change of ventilator set up, medical administration of supportive drugs, and close vital signs and hemodynamic monitoring. The surgeon de- cided to postpone the surgery. The patient was directly trans- ferred to intensive care unit (ICU) and ventilated with pos- itive pressure mode. After one day, the intensivist decided to wean him from mechanical ventilation and he was extu- bated successfully. Finally, the patient was discharged from the hospital with good general condition after two days from his admission. 3. Discussion The use of intrathecal fluorescein injection (in the subarach- noid space) for detecting the source of leakage, dates back to 1960, when Kirchner and Proud used this method to rec- ognize and locate CSF fistulas in the cranial base (11). Flu- orescein quickly diffuses out of the capillaries into the ex- travascular fluid compartments. In the circulation, fluores- cein moves mostly bound to plasma proteins and is metab- olized in the liver through glucuronidation. The monoglu- curonide has about 4.5% of the fluorescence of free fluo- rescein, and both are excreted through the kidney. While most fluorescein is eliminated after 24 hours, it can still be traced in urine up to a week after its infusion (12). The use- fulness of this test depends on the extent of the dural de- fect, rate of leakage, timing of the intrathecal injection, and rate of CSF turnover that could dilute or disperse the fluo- rescein. Reported complications of the solution’s injection, and thus limitations to its use, have ranged from mild to se- vere among which are tinnitus, headache, nausea and vom- iting, transient pulmonary edema, confusion, seizures, and coma, and death. Guimaraes R et al. reported that when they used a low dose of fluorescein (0.25cc of 5% solution) and diluted it with CSF and injected the solution slowly, com- plications did not happen (13). The reasons for the compli- cations were found in the method of administration, formu- lation of the solution, idiopathic reactions, and concentra- tion or dose of fluorescein (13-15). Side effects after the ad- ministration of intravenous fluorescein are uncommon and mostly harmless. Reactions more commonly seen include nausea and occasional vomiting. Severe reaction following intravenous fluorescein injection was observed in a patient who had an anaphylactic reaction (8). The exact mechanism of fluorescein-induced pulmonary edema following intrathe- cal injection is not known and it could happen due to multi- ple factors. Hypertension with overloading of the left ven- tricle and chemical alveolitis may cause pulmonary edema with fluorescein. A central neurogenic mechanism may play a role in the pulmonary changes (16). Although our patient had no underlying heart disease, bronchopulmonary infec- tion, or any other risk factor of pulmonary edema, intrathe- cal fluorescein injection could be considered as a causative factor for pulmonary edema. Anesthesiologists and medical practitioners should be aware of this serious adverse reaction of administrating this drug. 4. Conclusion: Medical practitioners should be aware of the complications of intrathecal fluorescein administration. 5. Appendix 5.1. Acknowledgements We are very thankful to Anesthesiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5.2. Authors contribution Faranak Behnaz (first author), research designer, Masih Ebrahimy Dehkordy (second author) writing the manuscript, Hamidreza Aziz Faresani (third author) research consultant and Mohammadreza Shahmohammadi (fourth author) re- search consultant. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2019; 7 (1): e18 Authors ORCIDs Faranak Behnaz: 0000-0003-2856-3975 Masih Ebrahimy Dehkordy: 0000-0001-5779-6204 Hamidreza Azizi Faresani: 0000-0002-4561-6066 Mohammadreza Shahmohammadi: 0000-0003-4803-8027 5.3. Conflict of interest None. 5.4. Funding and support None. References 1. Hawkins BT, Egleton RD. Fluorescence imaging of blood– brain barrier disruption. Journal of neuroscience meth- ods. 2006;151(2):262-7. 2. Javadi SAH, Samimi H, Naderi F, Shirani M. 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Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Case presentation: Discussion Conclusion: Appendix References