Case Report

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American Journal of Emergency Medicine

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American Journal of Emergency Medicine 33 (2015) 736.e1-736.e4

Combined intraaortic balloon counterpulsation and extracorporeal membrane oxygenation in 2 patients with

fulminant myocarditis?,??,?

Abstract

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an effective treatment for fulminant myocarditis (FM). However, VA- ECMO has a limited ability to facilitate left ventricular unloading. There- fore, increased afterload is still a significant concern, especially for those with diffuse myocardial damage and serious left ventricular dysfunc- tion. To our knowledge, there is no report concerning the use of these therapies to treat FM in China. This study investigates the efficacy of using intraaortic balloon counterpulsation to facilitate left ventricular unloading in patients treated with VA-ECMO. Here, we present 2 novel cases of Chinese women with FM treated with ECMO combined with intraaortic balloon counterpulsation. Both patients responded to treatment with improved pulsatile perfusion and left ventricular unloading. The first patient had a Complete recovery and exhibited nor- mal heart function after 2 years. Blood flow perfusion returned to nor- mal in the second patient; however, complications stemming from a hematogenous infection led to patient death. We found that the com- bined therapy induced pulsatile perfusion and sufficient left ventricular unloading and that the combined therapy was an effective treatment for FM patients with Electrical storm and left ventricular blood flow stasis. However, the combined therapy may increase the risk of catheter- related Bloodstream infections.

Fulminant myocarditis (FM) is a clinical syndrome that can develop from aggravated myocardial inflammation, which is often caused by viral myocarditis. Fulminant myocarditis manifests as severe arrhythmia, car- diogenic shock, and Acute congestive heart failure [1,2]. Fulminant myocar- ditis mortality is as high as 50% to 75% [1,2]. However, cardiac function can fully recover after effective hemodynamic management (such as mechan- ical circulatory support) once FM is diagnosed [1,2]. Venoarterial extracor- poreal membrane oxygenation (VA-ECMO) not only maintains sufficient coronary perfusion but also provides blood and oxygen supply to other im- portant organs [3]. Therefore, VA-ECMO has become one of the most effec- tive treatments available to rescue patients with FM [3,4].

? Authors’ contributions: Lan Chen designed the study. Wei Hu, Jun Lu, and Yin Zhu car- ried out the experiments and collected data. Jianrong Wang and Bingwei Liu analyzed the data and interpreted the results. Weihang Hu, Changwen Liu, and Lan Chen discussed

analyses, interpretation, and wrote the manuscript. All authors have contributed to, seen, and approved the manuscript.

?? The authors declare having no conflicts of interest regarding the design or outcomes

of this study.

? This study was supported by the Medical and Health Science and Technology Re-

search Program of Zhejiang Province (2011kyb062).

The primary concern when choosing to treat patients with VA-ECMO is that VA-ECMO has a limited ability to facilitate left ventricular unloading. This, especially in patients with diffuse myocardial damage and serious left ventricular dysfunction, can result in increased ventricu- lar diastolic pressure and impaired myocardial perfusion [3,4]. Venoarterial extracorporeal membrane oxygenation can also impede aortic valve opening, leading to serious consequences, including the delay of myocardial recovery and death [3,4]. Intraaortic balloon counterpulsation (IABP) has become the most commonly used measure for left ventricular unloading, and some studies have reported that ECMO combined with IABP could provide sufficient left ventricular unloading and improve myocardial metabolism in patients with severe coronary heart disease [5,6]. However, no study using these combined therapies to treat FM has been reported. Here, we present 2 novel cases of Chinese women with FM who were treated with ECMO and IABP. This study was approved by the Ethics Committee of Hangzhou First People’s Hospital.

A 25-year-old woman presented with a fever, Chest tightness, tachypnea, and fatigue that had persisted for 2 days and was hospital- ized on June 11, 2012. She denied a history of heart disease. Heart rate was 120 beats per minute with a galloping rhythm. Blood pressure was 100/62 mm Hg. A routine blood test showed white blood cells, 6.2 x 10^-9/L; neutrophils, 63.4%; and C-reactive protein, 15 mg/L. myocardial enzymes showed aspartate aminotransferase, 7 U/L; creatine kinase (CK), 217 U/L; creatine kinase isoenzyme (CK-MB), 14 U/L; lactate dehydrogenase, 161 U/L; and cardiac troponin I, 1.75 ug/L. Electrocardiogram (ECG) showed atrioventricular junctional tachycar- dia. The patient was diagnosed with viral myocarditis and admitted to the department of cardiology. After 20.5 hours, hemodynamic deterio- ration was observed (BP, 91/54 mm Hg with continuous administration of dopamine, 10 ug/kg per minute); and the patient was transferred to intensive care unit after undergoing endotracheal intubation. The pa- tient receivED treatments including the application of sufficient analge- sia and sedation, intravenous injection of ? globulin (0.40 g/kg) to improve the passive immunity and intravenous injection of methyl- prednisolone (40.0 mg) twice daily to reduce myocardial edema. After

30.5 hours, a continuous intravenous dopamine drip (15.00 ug/kg per minute) and dobutamine (30.00 ug/kg per minute) were required to maintain BP. Electrocardiogram showed sinus tachycardia with com- plete atrioventricular block and accelerated idioventricular rhythm. Echocardiography showed that the chamber size was in the reference range, ventricular wall motion was reduced, and left ventricular ejection fraction (LVEF) was 0.33. Cardiothoracic ratio was 0.45. Given these ob- servations, a clinical diagnosis of FM was made [1,2]. After the patient’s family agreed and gave informed consent, VA-ECMO was established

0735-6757/(C) 2014

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Fig. 1. Electrical storm after ECMO. A-D, Ventricular tachycardia occurred 4 times within 24 hours.

under general anesthesia by inserting an 18F tube into the femoral ar- tery to the bifurcation of the common iliac artery and inserting a 22F tube into the femoral vein to the entrance of the inferior vena cava. The initial flow rate of ECMO was 70 mL/kg. Six hours after circulation assistance began, the vasopressor dose was significantly reduced (dopa- mine, 3ug/kg per minute; BP, 95/78 mm Hg). Electrocardiogram showed sinus tachycardia and complete Right bundle branch block. On June 14th (28 hours after ECMO support began and 3 days after disease exacerba- tion), the patient was diagnosed with electrical storm (ES) after 4 distinct episodes of tachycardia in a 24-hour period (Fig. 1A-D). After restoration of sinus rhythm with drugs and electrical defibrillation, myocardial contractility was significantly decreased; and the left ventri- cle was overfilling and enlarged (Fig. 2A and B). Pulse pressure was less than 10 mm Hg (97/92 mm Hg), lactic acid (Lac) increased to a maximum of 4.00 mmol/L, and ECG showed repeated episodes of par- oxysmal ventricular tachycardia. Esmolol was continuously adminis- trated via vein micro pump. Left ventricular overload was identified, so IABP was emergently implanted at the patient’s bedside. After IABP

implantation, pulse pressure rose above 10 mm Hg, ES did not happen again, Lac decreased to 0.97 mmol/L, and left ventricular systolic func- tion was significantly improved (Fig. 3A and B). One hundred thirty- four hours after ECMO support was begun, the patient’s condition had improved sufficiently to meet the standards required to withdraw ECMO. Intraaortic balloon counterpulsation was removed 2 days later. The patient was discharged after 23 days in the hospital. Electrical storm did not reoccur, and the patient presented with normal heart function during the 2-year follow-up visit.

A 21-year old woman presented, during the 27th week of pregnancy, with a cough that had persisted for 3 days and chest tightness that had persisted for 2 days and was hospitalized on July 15, 2012. She denied a history of heart disease. Heart rate was 116 beats per minute with a gal- loping rhythm. Myocardial enzymes showed aspartate aminotransfer- ase, 185 U/L; CK, 704 U/L; CK-MB, 56 U/L; and cardiac troponin I,

12.39 U/L. ECG showed sinus tachycardia, Bidirectional ventricular tachycardia, and extensive ST-segment elevation with injury or ische- mic change. Echocardiography showed that the chamber size was

Fig. 2. Echocardiogram during ES. A, The Parasternal long axis view: left ventricle is enlarged (left ventricular end diastolic diameter, 5.6 cm), the apical end is swollen outward, interven- tricular septal thickness was 1.2 cm, ventricular wall motion decreased diffusely, LVEF was approximately 20%. B, Cloudy shadow was detected in the left ventricular cavity.

W. Hu et al. / American Journal of Emergency Medicine 33 (2015) 736.e1–736.e4 736.e3

Fig. 3. ECG and echocardiogram after implantation of IABP. A, ECG showed that blood flow perfusion recovered quickly to pulsatile flow perfusion. B, Left ventricle was slightly enlarged (left ventricular end diastolic diameter, 5.1 cm), interventricular septal thickness was 1.1 cm, ventricular wall motion was improved, LVEF was approximately 36%, and no thrombosis was detected in the left ventricular cavity.

within the reference range, and the cardiothoracic ratio was also within the reference range. A clinical diagnosis of FM was made [1,2]. The patient’s treatment included mechanical ventilation, sufficient analge- sia, and sedation for patient comfort; intravenous injection of ? globulin (0.40 g/kg) to improve passive immunity; and intravenous injections of methylprednisolone (40.0 mg) twice daily to reduce myocardial edema. However, the treatments had no obvious effect. On July 20th, a continu- ous intravenous drip of dopamine (20.0 ug/kg per minute) and dobuta- mine (40.0 ug/kg per minute) were being used to maintain BP. The pulse index Continuous cardiac output monitor showed that the cardiac index was 1.65 L/min per square meter, and ECG showed sinus tachycardia with complete atrioventricular block and ventricular escape leading to premature ventricular bigeminy. After the patient’s family agreed and gave informed consent, VA-ECMO was established under general anes- thesia by inserting a 16F tube into the femoral artery and inserting a 22F tube into the femoral vein. The initial ECMO rate of flow was 70 mL/kg. After 134 hours, continuous intravenous dopamine drip (3.0 ug/kg per minute) and nitroglycerin drip (0.53 ug/kg per minute) were used to maintain BP (90/76 mm Hg). Electrocardiogram showed sinus tachycardia with complete atrioventricular block and accelerated idioventricular rhythm. The patient was diagnosed with ES, after 3 events

occurred within 24 hours (Fig. 4A-C). After defibrillation and drug treat- ment, the ECG showed a ventricular escape rhythm (Fig. 4D), blood flow perfusion was a continuous nonpulsatile flow, and Lac increased to 4.5 mmol/L. Left ventricular overload was identified, so IABP was emergently implanted at the patient’s bedside. As a result, blood flow perfusion re- covered quickly to pulsatile flow perfusion, ES did not reoccur, LVEF in- creased from 0.20 to 0.30, and Lac decreased to normal levels. However, complete atrioventricular block was still present (see Fig. 5A and B). Eventually a catheter-related hematogenous infection occurred, and the patient died of multiple organ failure at 431 hours after ECMO.

In VA-ECMO, the cannula drains venous blood from the right atrium into a reservoir in vitro [7]. The blood is oxygenated in an oxygenator and returned to the femoral artery by a centrifugal pump [7]. Extracor- poreal membrane oxygenation can quickly restore normal Blood supply and oxygen supply and is typically used for FM patients who have not responded to Large doses of catecholamines or who have potentially fatal arrhythmias [8]. However, in severe FM patients with myocardial diffuse edema, injury, and decreased myocardial contractility, deteriora- tion can occur even with the support of ECMO [4-8]. In the present study, ES with blood flow stasis and increased Lac, indicating insuffi- cient ventricular unloading in the left ventricle, arose in 2 cases. It is

Fig. 4. Electrical storm after ECMO. A-C, Ventricular tachycardia occurred 3 times within 24 hours. D, After defibrillation and drug treatment, ECG showed sinus tachycardia with complete atrioventricular block and ventricular escape rhythm.

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Fig. 5. ECG before and after implantation of IABP. A, Electrocardiogram before implantation of IABP showed blood flow perfusion with continuous nonpulsatile flow, sinus tachycardia with complete atrioventricular block, and a ventricular escape rhythm. B, Electrocardiogram after implantation of IABP showed that blood flow perfusion recovered quickly to pulsatile flow perfusion. Ventricular escape rhythm was alleviated.

possible that the reverse flow generated by ECMO increased left ventric- ular afterload but had negligible unloading capability, leading to the ob- served symptoms [9-11]. In addition, the reverse flow impeded aortic valve opening, leading to left ventricular overfilling, expansion, exces- sive wall tension, decreased coronary perfusion, and increased myocar- dial oxygen consumption, which in turn induced ES [9-11].

The key treatment for left ventricular overfilling induced by ECMO is sufficient left ventricular unloading [6]. At present, left ventricular venting and IABP are common methods used to generate left ventricular unloading [9,11,12]. Left ventricular venting is usually used in Pediatric cases [12]. The catheter is percutaneously implanted into the left atrium through the right atrium and interatrial septum, and the outlet is con- nected to the vein tube of ECMO resulting in a decompression effect on the left ventricle [12]. Intraaortic balloon counterpulsation can generate left ventricular unloading because IABP changes the continuous nonpulsatile flow perfusion induced by ECMO to pulsatile perfusion [13]. In the 2 cases presented here, with the installation of IABP, continuous nonpulsatile flow perfusion turned into pulsatile perfusion, Lac decreased, ES seizure terminated, and ventricular wall contraction improved sug- gesting that IABP combined with ECMO was effective for left ventricular unloading. However, not all FM Patients supported by ECMO require the combined use of IABP and ECMO. Fulminant myocarditis patients with relatively normal pulse pressure, no cloudy shadow or vortex blood flow in the left ventricle (detected by echocardiography), and aortic valve opening during every left ventricular contraction were less prone to have left ventricular overfilling and expansion. In these cases, ECMO without IABP was sufficient. However, the second patient died of blood- stream infections, rather than serious health conditions. The possible rea- son was that combined IABP increased the opportunity of catheter-

related bloodstream infections due to the extra indwelling catheter.

In conclusion, IABP combined with ECMO was an effective treatment for FM patients with ES and blood flow stasis in the left ventricle. The combined therapy induced pulsatile perfusion and sufficient left ven- tricular unloading.

Weihang Hu, MD¹ Changwen Liu, MD¹ Department of Critical Care Medicine, Hangzhou First People’s Hospital, Zhejiang 310006, China

Lan Chen, MD Corresponding author at: Department of Electrocardiography Hangzhou First People’s Hospital, Zhejiang 310006, China Tel.: +86 13957161977; fax: +86 571 87914773

E-mail address: [email protected]

¹Contributed equally to this paper

Wei Hu, MD Jun Lu, MD Yin Zhu, MD

Jianrong Wang, MD Bingwei Liu, MD

Department of Critical Care Medicine, Hangzhou First People’s Hospital, Zhejiang 310006, China

http://dx.doi.org/10.1016/j.ajem.2014.10.043

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