Contrast medium induced pulmonary edema CASE REPORT Acute Non-cardiogenic Pulmonary Edema Associated with the Radiographic Contrast Medium Ioversol Honda Hsu1, Chih-Ming Lin1, Chung-Yen Tsai1, Shau-Bin Chou2, Tzong-Bor Sun1,3 Division of Plastic Surgery and Center for Hyperbaric Oxygen Therapy1, Department of Radiology2, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; Institute of Medical Sciences3, Tzu Chi University, Hualien, Taiwan ABSTRACT Ioversol is an iodinated, low-osmolality, nonionic contrast agent used in angiography. Life threatening non-cardiogenic pulmonary edema after intravenous administration of radiographic contrast medium is a rare event. We could find no report of ioversol-related pulmonary edema. We present a case of 65-year-old woman with diabetes mellitus and peripheral arterial occlusive disease who underwent angiography for evaluation of both lower limbs. Cold sweating, dyspnea, and lost of consciousness were noticed soon after 125 mL of ioversol injection. She was intubated immediately and chest radiograph showed severe pulmonary edema. After intensive mechanical ventilatory support, she recovered and was extubated 72 hours after the anaphylactic episode. Reports in the English literatures show that severe, life-threatening, adverse effects associated with radiographic contrast medium are rare. Our presenting case may be the first associated with the specific radiocontrast ioversol. Prompt differential diagnosis, aggressive venti- latory support, and avoid dehydration are essential to prevent a fatal outcome. (Tzu Chi Med J 2005; 17:273-277) Key words: contrast medium, pulmonary edema, ioversol, angiography, adverse effect physiological responses were collected and analyzed. INTRODUCTION Our experience in managing this rare case provides in- formation for future management of this idiosyncratic life threatening situation. Angiography is a common routine investigation in the diagnosis of peripheral arterial occlusive disease (PAOD). Most common adverse reactions include CASE REPORT nausea, palpitations and heat sensation. Severe reactions such as dyspnea, hypotension and cardiac arrest are re- A 65-year-old woman presented with right foot pain ported in 0.04% of all cases [1]. Life threatening non- for several months. She had visited many clinics, but cardiogenic pulmonary edema after intravenous admini- only intravenous analgesics were administered. Recently stration of radiographic contrast is a rare event. We necrotic skin changes were noticed over the medial and present a 65-year-old diabetic woman who presented lateral malleolar area. She was referred from a local clinic with a painful gangrene in the right foot for several for further treatment. She reported persistent continu- months. She sustained acute pulmonary edema during ous leg pain, which was partially relieved by dangling the angiography for evaluation of both lower limbs. The her legs over the side of the bed. There was no history initial symptoms/signs, resuscitation procedures, and of claudication as she was wheelchair bound due to left Received: October 19, 2004, Revised: November 10, 2004, Accepted: November 26, 2004 Address reprint requests and correspondence to: Dr. Tzong-Bor Sun, Division of Plastic Surgery and Center for Hyperbaric Oxygen Therapy, Buddhist Tzu Chi General Hospital, 707, Section 3, Chung Yang Road, Hualien, Taiwan Tzu Chi Med J 2005 17 No. 4 OTP H. Hsu, C. M. Lin, C. Y. Tsai, et al hemiparesis from a cerebral vascular accident 15 years coricosteroids (Solucortef 200 mg initially, and then 100 previously. She also had a history of diabetes mellitus mg/day). Blood pressure was maintained at 130-150/70- and hypertension with irregular medical treatment. She 90 mmHg without infusion of inotropic agents. The car- had no known allergies. Physical examination showed diologists were consulted. Cardiac echography revealed necrotic skin changes over the medial and lateral malleo- a left ventricle ejection fraction of 50%, moderate mi- lar area measuring 7 cm × 8 cm and 5 cm × 5 cm tral valve incompetence and normal wall motion. The respectively. Pulse was absent in both legs, and the femo- skin turgor was dry with continuous clear urine output ral pulses were also very difficult to palpate. A diagno- from the indwelling Foley catheter. In considering the sis of diabetic foot and peripheral arterial occlusive dis- underling myocardial ischemia from the routine ECG, a ease was made. Routine chest radiograph on admission dopamine infusion 3 µg/kg/hr was given alone with fluid was normal (Fig. 1A). The electrocardiogram on admis- resuscitation. After mechanical ventilation with PEEP sion demonstrated possible left ventricular hypertrophy and fluid replacement, she gradually improved over the by voltage criteria and ST-T depression which suggested next 72 hours as confirmed by serial chest radiographs possible chronic myocardial ischemia. The patient re- (Fig. 1C, D). Serial daily input/output amounts recorded called several episodes of palpitation and chest tightness. from the first day were 2213/2345, 3165/1635, and 3886/ Laboratory data revealed white blood cells 10100/µL, 3155 mL. Serum BUN and creatinine levels on the third hemoglobin 6.8 g/dL, platelets 532000/µL, erythrocyte day were 16 mg/dL and 1.5 mg/dL respectively. sedimentation rate (ESR) 70 mm/hr, blood urea nitro- Angiograms of the legs showed diffuse segmental ob- gen (BUN) 15 mg/dL, creatinine 1.4 mg/dL, glutamic struction of the femoral artery with formation of collat- oxaloacetic transaminase (GOT) 15 IU/L, and glutamic eral vessels. pyruvic transaminase (GPT) 6 IU/L. Angiography was done to evaluate the circulatory status of both lower limbs. In the Department of DISCUSSION Radiology, 125 mL of ioversol (Optiray 320, Mallinck- rodt Pharmaceuticals, St. Louis, MO, USA), an We presented a patient with PAOD and underlining iodinated, low osmolality, non-ionic contrast medium, myocardial ischemia who developed pulmonary edema was injected intra-arterially. While the angiography was after injection of ioversol for lower limb angiography. being performed, the patient complained of sudden The key to successful management of this challenging dizziness, nausea and chillness. Cold sweating and lost situation was to decide whether the pulmonary edema of consciousness was noticed. Oxygen saturation was was cardiogenic or non-cardiogenic, because these two 80% on 10 L/min of oxygen by face mask. She was in- conditions had different principles of treatment, in re- tubated immediately. After intubation, profuse pink, gard to fluid restriction or supplement. Thinking foamy sputum was secreted from the endotracheal tube. retrospectively, the etiology of pulmonary edema for this A chest radiograph was taken and she was then trans- case was not likely to be cardiogenic for the following ferred to the surgical intensive care unit (SICU) reasons. First, a central venous pressure measurement immediately. Her blood pressure was 130-150/70-90 of 1 mmHg suggested there was no right side heart mmHg and did not decrease throughout the period of failure. Second, the systemic blood pressure remained emergent management while she was in the radiologi- in the normal range without the aid of inotropic agents, cal department. so the possibility of left side heart failure was low. Third, Chest radiograph showed interstitial changes with the serum cardiac enzyme studies did not suggest acute acinar shadows in both lung fields (Fig. 1B). An elec- myocardial infarction. Fourth, more than 1000 mL of trocardiogram showed sinus tachycardia with ischemic crystalloid or colloid solution was infused every 8 hours changes in the inferolateral area, although there was no over the first 3 days after the episode. Together with chest pain. Arterial blood gases after intubation on 100% mechanical ventilatory support, this fluid resuscitation oxygen were pH 7.322, pCO2 42.5 mmHg, pO2 485 resolved the pulmonary edema despite cardiac size en- mmHg, HCO3 22.3 mmol/L, BE -3.1 mmol/L. Total cre- largement and the central venous pressure increased from atine kinase (CK 451 IU/L) and MB isoform (CK-MB 1 to 8 mmHg. Fortunately, the patient survived after 17 IU/L), as well as troponin I (0.04 ng/dL) suggested a proper treatment following initial recognition of ioversol low possibility of acute myocardial infarction. Her cen- induced non-cardiogenic pulmonary edema. tral venous pressure was 1 mmHg. She was placed on Non-ionic radiographic contrasts are used world- mechanical ventilation with positive end expiratory pres- wide. Ioversol, N,N'-Bis (2,3-Dihydroxypropyl)-5-[N- sure (PEEP). Fluid replacement was given, as well as (2-Hydroxyethyl)-Glycolamido]-2,4,6-Triiodoisoph- OTQ Tzu Chi Med J 2005 17 No. 4 Contrast medium induced pulmonary edema A B C D Fig. 1. Serial changes of the chest radiograph. (A) Chest radiograph of the patient on admission displays normal lung fields. (B) Chest radiograph immediately after angiography shows a butterflypattern, characterized by the central predominance of shadows with a clear zone at the peripheral lobes. (C) Chest radiograph shows improved lung fields after assisted mechanical ventilatory support for 24 hours. (D) Chest radiograph shows clear lung fields after assisted mechanical venti- latory support for 48 hours. Tzu Chi Med J 2005 17 No. 4 OTR H. Hsu, C. M. Lin, C. Y. Tsai, et al thalamide (molecular weight = 807.13), is an iodinated, nitric oxide (NO) production, and nitrovasodilators pro- low-osmolality, nonionic contrast agent, with an elimi- tect against