A case report of gadopentetate dimeglumine‐induced cardiac arrest: Resuscitation using extracorporeal membrane oxygenation

Abstract Gadopentetate dimeglumine (Gd‐DTPA) is commonly used for enhancement in magnetic resonance imaging, but rarely causes serious adverse reactions. The patient presented in this report had a cardiac arrest and multiple organ dysfunction syndrome within a short time after administration of Gd‐DTPA. Immediately after receiving an intravenous injection of Gd‐DTPA, the patient felt nausea and chest tightness, and developed systemic erythema. He was successfully treated using veno‐arterial extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy without any serious complications or neurological deficits. We report a patient who was successfully treated for Gd‐DTPA‐induced cardiac arrest with ECMO. Thus, ECMO may be an effective treatment for cardiac arrest secondary to anaphylaxis.

reactions to GBCA have an immunological etiology (Carr, 2016). It has also been reported younger patients are more prone to acute reactions (Okigawa et al., 2014).
The incidence of acute adverse reactions for gadopentetate dimeglumine (Gd-DTPA), a commonly used GBCA, is approximately 0.14%, most of which are mild and only require clinical observation without specific treatment; cardiac arrests are infrequent (Abujudeh et al., 2010). Although extracorporeal membrane oxygenation (ECMO) has been widely used to treat in-hospital cardiac arrest in patients undergoing non-cardiac surgery, including cardiac arrest secondary to anaphylactic shock (Simons et al., 2015;Zhang et al., 2015), reports involving the treatment of Gd-DTPA-induced cardiac arrest are limited.
Herein, we present a patient with Gd-DTPA-induced cardiac arrest who was effectively treated by emergency veno-arterial ECMO.

| C A S E REP ORT
A 58-year-old man weighing 70 kg was admitted to our hospital with penile cancer on April 27, 2021. Before undergoing a partial penectomy, an enhanced computed tomography (CT) with iohexol was obtained. A preoperative color Doppler ultrasound of the heart showed a small amount of mitral and tricuspid valve regurgitation.
The medical history was benign and he was taking no medications. There was no history of drug allergies or adverse reactions to contrast-enhanced CT. No medications were prescribed postoperatively at the time of hospital discharge on May 15, 2021.
A pelvic MRI was obtained on June 18, 2021 to evaluate inguinal and pelvic lymph node metastases after the penectomy. Immediately after receiving an intravenous injection of Gd-DTPA at 15 ml/min, the patient was nauseous, had chest tightness, and developed systemic erythema. The imaging examination was promptly terminated and mechanical ventilation was initiated. According to the patient, this was the first exposure to Gd-DTPA. Thus, the symptoms were considered to be an allergic reaction to Gd-DTPA. The stat blood IgE level was 1215 (normal value <100). Three minute later, the patient was dyspneic and cyanotic, the heart rate was 55 bpm, and the blood pressure was 82/55 mmHg. Epinephrine (1:1000 [0.5 mg]) was injected intramuscularly, a bolus of lactated Ringer's solution was infused intravenously, and oxygen was administered via tracheal intubation.
The patient developed ventricular fibrillation 8 min later. Bidirectional wave defibrillation (200 J) was delivered and cardiopulmonary resuscitation (CPR) commenced with chest compressions. Epinephrine (1 mg) was administered intravenously every 3 min. The cause of the in-hospital cardiac arrest was severe anaphylactic shock. Spontaneous circulation was not restored after 40 min. There are numerous reports of patients with anaphylactic shock and cardiac arrest caused by other drugs who were rescued by ECMO, thus ECMO was initiated. The left femoral artery and venous ECMO was established within 13 min (21Fr access cannulation and 17Fr return). Heparin anticoagulation was not used due to a coagulopathy after prolonged CPR and severe gastrointestinal bleeding (stress ulcer confirmed by gastroscopy).
To obtain a mean arterial pressure ≥65 mmHg, the ECMO flow rate was initially set at 3.0 L/min; however, due pipe jitter the ECMO flow rate only reached 2.0 L/min, at which time the blood pressure was only 63/51 mmHg, so high doses (2.0 μg/kg/min) of norepinephrine and epinephrine were administered to maintain a mean arterial pressure of ≥65 mmHg. During this period, the patient had circulatory instability (left ventricular ejection fraction = 15%) with pulmonary edema and metabolic acidosis. The arterial blood gas results were as follows: pH, 7.086; bicarbonate ion (HCO 3 ), 12.3 mmol/L; standard base excess (SBE), −17.1 mEq/L; and lactate, 19 mmol/L.
After 1 h on ECMO, ventricular fibrillation persisted despite two attempts at electrical defibrillation. Continuous renal replacement therapy (CRRT) combined with large amounts of plasma and albumin (i.e., heparin-free anticoagulation strategy) were administered to stabilize the circulation, while reducing capillary exudation. Several hours later, the lactic acid and vasoactive drugs were progressively decreased. Electrical defibrillation was attempted again, which restored a spontaneous heart rhythm (128 beats/min) after 4 h of ECMO. The ECMO flow rate was set at 1.8 L/min. The doses of norepinephrine and epinephrine were 2.0 and 1.5 μg/kg/min, respectively.
The blood pressure was 118/63 mmHg. The arterial blood gas results were as follows: pH, 7.46; HCO 3 , 27.3 mmol/L; SBE, −3.7 mEq/L; and lactate, 2.9 mmol/L. Forty-eight hours after ECMO, the patient had recovered completely without any serious complications or neurological deficits, and was discharged on hospital day 10. No further immunological testing was performed. There was no allergy-related discomfort prior to hospital discharge and no discomfort at the subsequent outpatient follow-up evaluation.

| DISCUSS ION
GBCA is considered to be very safe in clinical practice (Abujudeh et al., 2010;Zhang et al., 2015). Use keywords as below to search on PubMed, dated until June 28, 2022: "GBCA AND acute adverse reaction," "gadopentetate dimeglumine AND acute adverse reaction," "gadobutrol AND acute adverse reaction," "gadoterate meglumine AND acute adverse reaction," "gadopentetate dimeglumine AND cardiac arrest." After reading the titles and abstracts, the reports about severe or serious acute reactions were selected and summarized in Table 1.
As shown in Table 1, the incidence of GBCA (including Gd-DTPA)associated acute severe reactions is 0.003%-0.04%. Only five patients with cardiac arrest due to the use of GBCA have been reported as of June 28, 2022, and epinephrine and CPR are common treatment strategies for such cases (highlighted in yellow, Table 1); ECMO was not discussed as a rescue strategy. Among the five patients with cardiac arrest, four were revived and one died; however, the rescue details were not disclosed (highlighted in yellow, 4/158796, 0.003% The fourth case was a 9-year-old boy who became combative during an MRI with urticaria, wheezing, and desaturation (oxygen saturation in the 80s) occurring after injecting 10 ml gadoteridol He responded to epinephrine, albuterol, diphenhydramine, and decadron; after stabilizing and recovering from anesthesia, the patient was discharged home This study raises the possibility that non-ionic linear gadolinium-based contrast agents and gadopentetate dimeglumine may have fewer severe immediate adverse events compared with gadobenate dimeglumine Jordan & Mintz, 1995 Case report She became very short of breath after injection; pulse rate decreased and blood pressure increased. Full cardiopulmonary arrest ensued; finally, she was died Epinephrine (0.3 mg, 1 g/1000 ml) was administered subcutaneously, as no IV site was immediately available; atropine (1 mg) IV was also given; the patient did not respond to these measures, became progressively diaphoretic and cyanotic, and was soon in full respiratory arrest; full cardiopulmonary arrest ensued, and cardiopulmonary resuscitation was initiated; resuscitative efforts were continued in the emergency department but were unsuccessful; autopsy showed severe bullous emphysema; focal, moderately severe (60%) atherosclerosis of the left coronary artery was present The presumed cause of death is an anaphylactic reaction with associated bronchospasm; radiologists and MR imaging personnel should therefore remain alert to the possibility of severe, rarely fatal, reactions to gadolinium-based contrast agents, especially in patients with a history of asthma or other chronic respiratory disease.

TA B L E 1 (Continued)
dramatic I-type allergic reaction (IgE-mediated) to Gd-DTPA, which is similar to the report by Schiavino et al. (Schiavino et al., 2003). Our patient rapidly progressed to ventricular fibrillation 8 min after Gd-DTPA use. A spontaneous circulation was not restored, despite external chest compressions, epinephrine injections, and defibrillation. Without ECMO support, the outcome would most likely have been death.
ECMO has been shown to be effective in providing circulatory support to patients in cardiogenic shock or cardiac arrest by providing respiratory support alone, respiratory and right ventricular support, or full cardiopulmonary support (Ratnani et al., 2018;Simons et al., 2015).
Early ECMO initiation provides benefits, such as delivering appropriate oxygenation and/or tissue perfusion, and providing lung and heart rest. The use of ECMO in the early stages of trauma may increase the risk of bleeding due to systemic heparin anticoagulation, especially in patients with intracranial or active systemic bleeding (Wang et al., 2020). Therapeutic heparin may increase the risk of bleeding. CRRT is indicated for patients with acute kidney injury who are hemodynamically unstable, thus allowing precise volume control, correction of metabolic disturbances, and stable acid-base and electrolyte correction (Karkar & Ronco, 2020). In addition, CRRT was implemented in a patient who was diagnosed with an acute kidney injury (AKI) to correct metabolic disturbances and control volume (Karkar & Ronco, 2020). In addition, CRRT may decrease internal contrast media levels, thereby alleviating allergic reactions (Song et al., 2021).
An expedited allergy work-up with skin testing and assessment of premedication data may help prevent an allergic reaction to GBCA, as shown in Table 1. The reported patients with cardiac arrest due to GBCA are limited, thus the underlying mechanism and effective prevention strategies have not been established. Patients with atherosclerosis, cardiovascular disorders, or chronic respiratory diseases warrant a thorough evaluation (Table 1).

| CON CLUS ION
In conclusion, we report the first case of successful treatment of

ACK N OWLED G M ENTS
Declared none.

FU N D I N G I N FO R M ATI O N
This case report was supported by Project of Zhejiang Provincial Department of Health (2021KY1192) and Quzhou Bureau of Science and Technology (2022K71).

CO N FLI C T O F I NTE R E S T
The authors declare no conflicts of interest, financial, or otherwise.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available on request from the corresponding author.

CO N S E NT
The patient has consented to submission of the case report to the journal.