MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

------------------------------------------------- BUI VAN CUONG RESEARCH ON CRICULATION SUPPORT EFFECTS OF

VENO ARTERIAL EXTRACORPOREAL MEMBRANE

OXYGENATION (VA-ECMO) IN TREATMENTING ACUTE

MYOCARDITIS PATIENTS Speciality: Anesthesiology

Code: 62720122

ABSTRACT OF MEDICAL PHD THESIS

Hanoi – 2021

THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

Supervisor:

1. Ass Prof. PhD. Le Thi Viet Hoa 2. Ass. Prof. PhD. Dao Xuan Co

Reviewer 1: Ass Prof. PhD. Mai Xuan Hien

Reviewer 2: Ass Prof. PhD. Ha Tran Hung

Reviewer 2: Ass Prof. PhD. Hoang Bui Hai

This thesis will be presented at Institute Council at: 108 Institute of

Clinical Medical and Pharmaceutical Sciences

Day Month Year

The thesis can be found at:

Institute of Clinical Medical and 1. National Library of Vietnam 2. Library of 108 Pharmaceutical Sciences 3. Central Institute for Medical Science Infomation and Tecnology

1

INTRODUCTION

Myocarditis is defined as an inflammation of the myocardium

with the most reason caused by virus. The severe acute myocarditis

such as fluminant myocarditis can lead to cardiogenic shock, life

threatening arryhythmia and death. With the unrespond patients, the

more use vasopressors and inotropic drugs, the more oxygen demand

of myocardium that make the heart injury unrecoverable and the

patients die. Peripheral veno arterial extra corporeal membrane

oxygenation (VA-ECMO) is a form of cardiopulmonary life support,

where blood is drained from the venous system (inferior vena cava or

superior vena cava) circulated outside the body by a centrifugal

pump, and went through oxygenator for oxygenating and CO2 eliminating then reinfused into the circulation throughout arterial

system (most common abdominal arotic artery). Thanks to VA-

ECMO stopped vicious circle of pathogenesis and waiting of

myocardial recovery. Nowadays, the studies showed that VA-ECMO

has efficacy on acute myocarditis with the 60-70 % survival rate. In

Viet Nam, there have been a fews studies about this issue, therefor

we perfrom the study:

“Research on circulation support effects of veno-arterial

extracorporeal membrane oxygenation (VA-ECMO) in treatmenting

acute myocarditis patients” with two objectives:

1. Evaluate the improvements of circulation, arterial blood gas,

organ function of veno arterial extracorporeal membrane

oxygenation (VA-ECMO) in treatmenting acute myocarditis patients.

2

2. Remark some prognostic factors of mortality and

complications of veno arterial extracorporeal membrane oxygenation

for acute myocarditis patients.

* The urgency of study:

Acute myocarditis is a acute myocardium injury with clinical

presentations of the disease range from nonspecific systemic

symptoms that it resolves spontaneously to fulminant cardiogenic

shock, life threatening arryhythmias such as ventricular tachycardia,

ventricular defibrillation and cardiac arrest. It had high mortality

approximately 50% and it is common in young people. Nowadays

the studies showed that VA-ECMO has efficacy on acute

myocarditis, ICU in Bach Mai hospital is implementing VA-ECMO

for acute myocarditis but there have been a fews studies about this

issue, therefore we perform this study for evaluating the efficacy and

complications of veno arterial extra corporeal membrane

oxygenation (VA-ECMO) in treatmenting acute myocarditis patients.

* The novelty of study:

- The results of study showed that the VA-ECMO was highly

effective in acute myocarditis patients having complications

cardiogenic shock and life threatening arryhythmias.

- The results of study revealed some prognostic factors of

mortality in VA-ECMO supported acute myocarditis patients.

- The results of study found that the most bleeding complication

was ECMO cannula site.

* The lay-out of thesis: There are 127 pages including introduction

2pages, overview 36 pages , materials and methods 21page, results

25 pages, discussion 40 pages, conclusion 2 pages, and request with

31 tables, 10 charts and 10 graphs in suitable structure. There were

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119 references including 2 Vietnamese references and 117 English

references.

CHAPTER 1: OVERVIEW

1. ACUTE MYOCARDITIS

1.1. Definition and pathophysiology

Myocarditis is defined as an inflammation of the cardiac

muscle. Acute myocaditis account for 6% cause cardiogenic shock.

Clinical presentations of the disease range from nonspecific systemic

symptoms that it resolves spontaneously to fulminant cardiogenic

shock, life threatening arryhythmia and cardiac arrest. Based on

observations of acute myocarditis due to coxsackie virus in humans

as well as in mice, acute myoarditis caused by virus is a continuum

of distinct disease processes including 3 phases. The first phase is

viral infection and replication in myocardium. Viral proteolysis and

cytokine activation cause myocardial damage leading apotosis. It is

difficult to recognise this phase by clinical sign because of the

patients having asymptomatic or unspecific clinical. The second

phase involving the host’s immune activation, it simulates cellular

and humoral immune responses that reduces viral replication leading

to myocardial recovery. However, immune activation is not

decreasing possibly due to the activation of T cells against

myocardium throughout the peptides of viruses. This leading to

release cytokines such as tumor necrosis factor (TNF), IL-1, and IL-

6 resulting in more myocardium damage. Overactivation of cellular

immunity or viruses are not completedly eliminated and continue

replicating leading the third phase. This phase, left ventricle was

enlarged due to remodeling phenomenon, it causes left ventricle

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function disorder and heart failure. If the inflammatory decreases, the

left ventricle function will improved but the continuing inflammatory

leading to dilated cardiomyopathy.

1.3. Main treatment

1.3.1. Respiratory support: depend on patients that need nasal

cannula, mask cannula, non invasive ventilation and invasive

ventilation.

1.3.2. Circulation support: fluid resuscitation, vasopressor agents

1.3.3. Mechanical circulatory support

Mechanical circulatory support is indicated if the

cardiogenic shock patients did not response with conventional

treatment. VA-ECMO is the best choice in this acute myocarditis

patients complicated cardiogenic shock and life threatening

arryhythmias.

- VA- ECMO systems

Peripheral veno arterial extracorporeal membrane

oxygenation (VA-ECMO) is a form of cardiopulmonary life support,

where blood is drained from the big venous system, circulated

outside the body by a centrifugal pump, and then reinfused into the

circulation throughout big arterial system. ECMO system including

ECMO machine, circuit and cannula. The blood goes through

oxygenator eliminated CO2 and oxygenated and return to patient. The advantage of ECMO system can setup quickly, bedside for

supporting patients for some weeks.

1.4. Efficacy of ECMO study on acute myocardtis patients

According to Yih, the fours survivors accouting for 80 percents

were discharged and the TnT level declined to the low level within

3 days might be an indicator of good recovery but the study

5

limitation was the small patient numbers so it was difficult to reach

statistical significance. Chen study showed that 14 (93.3%) of the

15 patients could be weaned off VA-ECMO, and the survival rate

was 73.3% (11 of 15) without transplantation. One of four patients

died of severe brain damage because of prolonged cardiopulmonary

resuscitation. The survival rate in Matsumoto study 70.2% (26 of

37 patients), four of fifteen unweaned group switched from VA-

ECMO to left ventricle assist device were survival after heart

tranplantation or continuous treatment. Aoyama study revealed the

survival rate was 57.7% and EF before ECMO and acute kidney

injury complication of the mortality group were more severe. The

survival rate of Diddle study was 61%, but the patients having

acute kidney injury had higher mortality with OR 3.6, CI 1.4-9.3,

CI 95%. According to X.Liao, 78.8% surviaval rate, before ECMO

serum lactate concentration was very high. The patients having

high quantities of blood product transfusion, renal failure,

encephalorrhagia, high bilirubin levels, or multiple organ failure

(MOF) during ECMO were associated with poor outcome. Wigfield

study found that main factor caused death in VA-ECMO patients

was MOF.

CHAPTER 2: MATERIALS AND METHODS

2.1. Inclusion criteria

a/ The patients suffered from acute myocarditis by 2013 the

European Society of Cardiology’s criterion were admitted ICU Bach

Mai hospital from 2015-2018.

- Clinical presentations new onset acute chest pain, pericarditic, or

pseudo-ischaemic or worsening of: dyspnoea at rest or exercise,

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and/or fatigue, with or without left and/or right heart failure signs

and/or unexplained arrhythmia symptoms and/or syncope, and/or

aborted sudden cardiac death or unexplained cardiogenic shock

- Newly abnormal 12 lead ECG or elevated TnT/TnI cardiac

markers, functional and structural abnormalities on cardiac imaging

(echo/angio/CMR).

- Exclusion criteria: angiographically detectable coronary artery

disease (coronarystenosis ≥50%); known pre-existing cardiovascular

disease or extra-cardiac causes that could explain the syndrome

b/ And suffered from cardiogenic shock by 2012 the European

Society of Cardiology’s criterion

- Hypotension: systolic blood pressure < 90mmHg for 30

minutes, or vasopressors required to achieve a blood pressure ≥ 90

mmHg

- Evelated left ventricular filling pressure: pulmonary congestion

or adequate or elevated filling pressure (wedge pressure > 20 mmHg)

- Signs of impaired organ perfusion (at least one of the

following): altered mental status, cold, clammy skin, oliguria,

increased serum lactate levels.

c/ And IE ≥ 40 g/kg/minutes and/or life threatening criteria such as

ventricular tachycardia, ventricular fibrillation or cardiac arrest.

2.1.2. Exclusion criteria

- The aortic artery dissection patient

- Patient or patient’s family doesn’t agree with taking part the

study

- Cardiogenic shock in HIV-AIDS or end state cancer patients

2.3. Methods

2.3.1. Study design: progressing, intervention and before-after study

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2.3.2. Sample size: Formular N= 2C x (1-r)/ (ES)2

N: estimated sample size, C: constant of type I, II error, r:

relative coeficient, là hệ số tương quan giữa 2 đo lường, ES : effect

size . In our study : C = (Zα/2 + Zβ) 2 with α = 0.05, β = 0.20 thì C =

7,85 , r= 0,6 and ES= 0,41 (current study mortality rate is 50%, expection

mortality rate 30%) => N= 37. With an estimated 10% loss rate so the

sample size was 37/0,9 = 42 patients.

2.3.5. The variables of study

2.3.5.1. Charateristics of patient and ECMO parameters

- Name, family name, age, gender, weight, past medical history

(healthy, heart failure, hypertension, COPD), fever, dyspnea, chest

pain, cold, clammy skin, cardiac arrest, vasopressor and inotropic

dose, IE index, SAVE score, APACHE II score. ECG on admission,

ventricular fibrillation, ventricular tachycardia, ventricular

extrasystole, third-degree AV block, atrial rhythm, sinus rhythm.

ECMO cannulation techniques (percutaneous or surgery

cannulation). The duration of ECMO, the number of membranes,

CO, flow, FiO2 of ECMO. 2.3.5.2. The improvenments of circulations

-Pulse, MAP, pulse pressure, vasopressor and inotropic dose,

ECG, CK, CKMB, Troponin T, proBNP EF, Dd, Ds, right heart

diameter before ECMO, day 2, day 3, day 4, day 5 and stopped

ECMO

- LVOT_CO, VTI, TAPSE on stopped ECMO.

2.3.5.3. The improvement of arterial blood gas

-ABG: pH, pCO2, PaO2, HCO3, lactate before ECMO, day 2, day 3, day 4, day 5 and stopped ECMO

2.3.5.4. The improvement of organ function

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SOFA score before ECMO, day 2, day 3, day 4, day 5 and

stopped ECMO

2.3.5.5. Some prognostic factors of mortality

SOFA score, APACHE II score, SAVE, pulse pressure on day 5,

cardiac arrest and serum lactat associated with mortality rate.

2.3.5.6. Some comlications of VA-ECMO

- Lower limb arterial thrombosis complication on the ECMO

cannulation site

- Infection:

+ General infection: temperature, white blood cell, procalcitonin

before ECMO, day 2, day 3, day 4, day 5 and stopped ECMO

+ Infection of ECMO cannula site,

- Neurologic complication

- Bleeding: ECMO cannula site, central line site, arterial line,

gastrointestinal bleeding. Coagulation factors associated

complications such as PT, APTTs, fibrinogen, D-dimer, ethanol test

before ECMO, day 2, day 3, day 4, day 5, stopped ECMO and one

day later stopped ECMO.

- Heparin dose: bolus dose, day 1, day 2, day 3, day 4, day 5 and

stopped ECMO

- Acute pulmonary edema, CRRT

2.4. The definition of score, criteria in research

- CDC Criteria of Surgical Site Infection

Date of event occurs within 30 days after any NHSN operative

procedure and involves only skin and subcutaneous tissue of the

incision and patient has at least one of the following: a. purulent

drainage from the superficial incision. b. organism(s) identified from

an aseptically-obtained specimen from the superficial incision or

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subcutaneous tissue by a culture or nonculture based microbiologic

testing method which is performed for purposes of clinical diagnosis

or treatment (for example, not Active Surveillance Culture/Testing

(ASC/AST)). c. superficial incision that is deliberately opened by a

surgeon, physician or physician designee and culture or non-culture

based testing of the superficial incision or subcutaneous tissue is not

performed AND patient has at least one of the following signs or

symptoms: localized pain or tenderness; localized swelling;

erythema; or heat. d. diagnosis of a superficial incisional SSI by a

physician or physician designee.

- Lower limb arterial thrombosis complication on the ECMO

cannulation site: found durring stopped ECMO or ultrasound.

- neurologic complications: cerebral haemorrhage and cerebral

infarction: found signs on MRI or CT

- Bleeding: the bleeding clinical signs of ECMO cannula site, central

line site, arterial line. gastrointestinal bleeding based on clinical signs

and endoscopy.

- Acute kidney injury: RIFLE classification

- Organ failure: SOFA score

2.5. Collect data for the study following the medical report form

2.6. Data analysis: following medical statistic method

CHAPTER 3: STUDY RESULTS

3.1. Characteristics of patients

From 2015-2018, there were 54 patients having full criteria’s

for inclusion: female 66.7% (36 patients), average age 35.6  11.17

years old (min 18- max 67), 18 cardiac arrest patients (33.3%).

10

Table 3.1: Some indexes of patients before ECMO

p

Total ( X ±SD)

Survival ( X ±SD)

Non-survival ( X ±SD)

APACHE II

10.3±5.45 (n=54) 8.9±4.43 (n=44) 16.4±5.52 (n=10) <0.05

7.8±2.68 (n=54) 7.4±2.68 (n=44) 9.6±2.01(n=10) <0.05

SOFA before ECMO Lactat (mmol/l)

7.60±4.47 (n=54) 7.2±4.08 (n=44) 9.05±5.94 (n=10) >0,05

EF (%)

33.2± 13.55 39.8± 15.46 (n=8) >0.05

SAVE

<0.05

Troponin T (ng/L)

>0.05

<0.05

34.3±13.92 (n=49) Median: 2.5 (n=54) Median 4409 (n=53) Median 35 (n=18)

Median 5 (n=44) Median 4409 (n=43) Median 30 (n=11)

Median -3 (n=10) Median 4756 (n=10) Median 40 (n=7)

The duration of cardiac arrest (minutes)

Remark: SOFA score, APACHE II score, serum lactate,

Troponin T profoundly increased and EF dramatically decreased, the

median time of cardiac arrest was 31 minutes, these showed that the

patients having severe myocardial injury and cardiogenic shock.

Chart 3.1: The duration of ECMO and the number of membrane

Remark: 95% patients were supported VA-ECMO within 2

weeks, almost cases only used one membrane.

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3.2. Objective 1: The improvements of circulation, arterial blood

gas, organ function

3.2.1. The improvenments of circulations

Chart 3.2: Change in blood pressure, mean arterial pressure,

inotropic equivalents during ECMO

Remark: MAP improved on VA-ECMO day 2 and stably

maintained during ECMO, pulse pressure was enormous fallen after

ECMO support and returned on day 5 and significantly rised on

stopped ECMO day. IE index rapidly delined after ECMO

commencement.

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Table 3.2: Change in serum lactate during ECMO

Median (Interquartile range)

p

Before ECMO (n=54)

7.55 (3.5-10.9)

ECMO day 2 (n=52)

1.90 (1.4-2.7)

<0.05

ECMO day 3 (n=50)

1.85 (1.1-2.4)

<0.05

ECMO day 4 (n=50)

1.75 (1.1-2.7)

<0.05

ECMO day 5 (n=47)

1.56 (1.0-2.4)

<0.05

Stopped ECMO (n=54)

1.35 (0.8-2.5)

<0.05

*p<0.05 compare with T0 with others

Remark: serum lactate concentration significantly dropped

after ECMO

Chart 3.3: The change in ECG during ECMO Remark: The result showed that ventricular tachycardia, third-

degree AV block and sinus rhythm were nearly 53%, 40% on

admission respectively. 31.5 % patients had elevated ST segment.

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Table 3.3: Change in cardiac marker during ECMO

Troponin T (U/L)

Median

p

Interquartile range

4409.0 (n=53)

(2755.0-7369.5)

Before ECMO

3690.0 (n=53)

(1535.5-6744.0)

<0.05

ECMO day 2

2320.0 (n=51)

(1010.0-5385.0)

<0.05

ECMO day 3

1420.0 (n=51)

(450.0-3450.0)

<0.05

ECMO day 4

840.0 (n=46)

(302.0-2162.2)

<0.05

ECMO day 5

259.0 (n=54)

(115.8-1810.0)

<0.05

Stopped ECMO

*p<0.05 compare with T0 with others

Remark: Troponin T remarkably decreased from day 3 to stopped

ECMO day.

p Table 3.4: Change in EF (%) during ECMO ±SD) Min-max

Before ECMO (n=49) ECMO day 2 (n=53) ECMO day 3 (n=52) ECMO day 4 (n=51) ECMO day 5 (n=47) Stopped ECMO (n=51) 10-72 10-41 11,5-63 6.7-55.0 12-60 17-72 <0.05 <0.05 <0.05 >0.05 <0.05 ( 34.313.92 22.06.67 24.19.96 27.19.74 33.012.5 47.713.91 *p<0.05 compare with T0 with others

Remark: EF significantly reduced after ECMO support and returned

on stopped ECMO day.

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3.2.2. The improvement of arterial blood gas

Table 3.5: The change in arterial blood gas during ECMO

PaO2 (mmHg) Median (IQR)

pH ( X ±SD)

Before ECMO ECMO day 2 ECMO day 3 ECMO day 4 ECMO day 5 Stopped ECMO

133.5 (n=52) (80.2-304.2) 205,5 (115.2-331.7)* 146.0 (n=50) (113.7-249.7) 140.5 (n=50) (106.0-140.5) 141.0 (n=47) (97.0-208.0) 153.5 (n=54) (104.7-213.2)

PCO2 (mmHg) ( X ±SD) 32.614.30 (n=54) 32.66.30 (n=52) 35.67.67* (n=50) 34.96.60* (n=50) 35.56.99* (n=47) 35.46.62 (n=54)

HCO3 (mmol/l) ( X ±SD) 16.14.88 (n=53) 23.14.31* (n=52) 26.05.40* (n=50) 26.85.31* (n=50) 27.35.01* (n=47) 25.36.66* (n=54)

7.300.14 (n=54) 7.450.09* (n=52) 7.470.09* (n=50) 7.490.08* (n=50) 7.490.06* (n=47) 7.440.12* (n=54) *p<0.05 compare with T0 with others

Remark: Metabolic acidosis was tremendous improved after ECMO

3.3. The improvement of organ function

Table 3.6: Change in SOFA score during ECMO

Min-max

p

Before ECMO (n=54)

4-17

( X ±SD) 7.82.68

ECMO day 2 (n=53)

>0.05

4-17

8.62.76

ECMO day 3 (n=52)

<0.05

4-17

9.22.86

ECMO day 4 (n=52)

<0.05

4-17

9.62.44

ECMO day 5 (n=47)

<0.05

5-16

9.82.74

Stopped ECMO (n=54)

<0.05

5-23

9.93.26

<0.05

0-10

4.52.31

SOFA after stopped ECMO 1 day (n=44)

*p<0.05 compare with T0 with others

Remark: SOFA score did not go down during VA-ECMO even

slightly increase but profoundly decreased after stopped ECMO one

day.

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3.3. Objective 2: Some prognostic factors of mortality and

complications of VA-ECMO

3.3.1. Some prognostic factors of mortality

- The survival rate was 82.14%

3.3.1.1. Cardiac arrest associated with mortality rate

Table 3.7: Cardiac arrest associated with mortality rate

OR CI-95%

Survival (n=44) 11 (25%)

Non-survival (n=10) 7 (70%)

7.14

Cardiac arrest

0.03-0.65

Non- cardiac arrest

33 (75%)

3 (30%)

Remark: The mortality rate in cardiac arrest patients was 7,14 times

as many as the mortality rate in non-cardiac arrest patients.

3.3.1.2. Pulse pressure associated with mortality rate

Table 3.8: Pulse pressure associated with mortality rate on day 5

OR

CI-95%

Survival n (%)

Non-survival n(%)

>20

31 (96.8)

1 (3.2)

12.5

0.01-0.8

<=20

10 (71.4)

4 (27.8)

Pulse pressure on day 5 (mmHg)

Remark: The mortality of patients having pulse pressure less than

20 mmHg on ECMO day 5 was 12.5 times higher than patients

having pulse pressure greater than 20 mmHg

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Chart 3.4: SAVE and serum lactat associated with mortality

Remark: SAVE score with cut-off -8 point having sensitivity 87%,

specificity 90% and AUC 0.934 for mortality prediction

3.3.2. Some complications of VA-ECMO

Bleeding site

Arterial line site

Central line site

GI bleeding

Cerebral hemorrhage

Time

20 (37) 31 (57.4) 32 (59.3) 33 (61.1) 31 (57.4) 28 (51.9)

2 (3.7) 3 (5.6) 2 (3.7) 3 (5.6) 6 (11.2) 5 (9.3)

n=(%) 10 (18.5) 17 (31.5) 10 (18.5) 16 (29.6) 17 (31.5) 25 (46.3)

0 (0) 2 (3.8) 0 (0) 2 (3.8) 0 (0) 0 (0)

0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)

Table 3.9: Bleeding complications ECMO cannula site

ECMO day 1 ECMO day 2 ECMO day 3 ECMO day 4 ECMO day 5 Stopped ECMO

Remark: The most bleeding complications were ECMO cannula site

and arterial line site, the highest bleeding rate on ECMO day 4 and

on stopped ECMO day were 61.1%, 46.5% respectively.

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Chart 3.5: Lower limb arterial thrombosis complication

Remark: Lower limb arterial thrombosis complication during

stopped ECMO was twice as many as after the arterial thrombosis

complication stopped ECMO. There was not signicantly different the

lower limb arterial thrombosis rate between percutaneous ECMO

cannulation and surgery ECMO cannulation.

3.3.2.5. Acute pulmonary edema and neurologic complications

- Acute pulmonary edema: 16/54 (29.6%)

- Cerebral infarction: 01 case

CHAPTER IV DISCUSSION

4.1.1. Characteristics

54 acute myocarditis patients with mean age 35.6 (min 13-max

67), 31-50 range having 57.4%, and female accounted for 66.7%,

the results was similar to the other authors. Almost acute

myocardisits patients were female, some studies showed that the

male-female ratio may be different but young people suffered from

acute myocarditis higher than the elder did.

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The results showed that almost patients with cardiogenic shock

complicated multiple organ failure syndrome (MOFS), their

APACHE II, SOFA score and serum lactate were 10.3  5.45, 7.8

2.68, 7.6  4.47 mmol/l, respectively. The high serum lactate

concentration reflected the severe cardiogenic schock leading tissue

hypoperfusion. Troponin T profoundly increased to 4409.0 ng/L

because of severely myocardial necrosis. Although the patients was

supported high dose vasopressors, EF was only 34.313.92 (%). 18

patients (33.3%) having cardiac arrest.

4.1.2. The ECMO duration and number of ECMO membrance

ECMO duration in this study was 7.6 2.9 days, one patient did not

respone, did not maintain blood pressure and died that only supported

ECMO more than one day. Subgroup analysis showed that 34 patients

(63%), 17 patients (31.4%) and 3 patient were supported less than 7

days, from 8- 14 days, greater than 14 days respectively. According to

these results, the ECMO duration of nearly two third acute myocarditis

patients within one week.

4.2. Objective 1: The improvements of circulation, arterial blood

gas, organ function

4.2.1. The improvements of circulation

Desipte high dose vasopressor with median 70 μg/kg/minute,

mean arterial pressure’s patients before ECMO 62.4  24.60 mmHg.

After ECMO, mean arterial pressure (MAP) incresased significantly

that was 76.79.93 mmHg. Before ECMO, pulse pressure was

33.714.85 mmHg and it dramatically decreased with median 14 on

ECMO day 2, after that is returned from day 3, especcially highest

value on stopped ECMO day.

19

Before ECMO the serum lactate concentration median was

7.55 mmol/l and markedly decreased on day 2 with median 1.9

mmol/l which demostrated better tissue perfusion and higher MAP.

There were 18 ventricular arrhythmia patients (33.3%), 3 ventricular

extrasystole patients, 11 third-degree AV block patients (20.4%) and

22 sinus rhythm patients on admission. It mean that nearly a half

patients having life threatening arrhythmia. The median of Troponin

T profoundly decreased from 4409.0 ng/L on admission to 259.0

ng/L on stopped ECMO day. It reflected that the myocardial necrosis

was deacreasing.

Although the patients was supported high dose vasopressorss, EF

was only 34.313.92 (%) so the actual EF value without vasopressors

was very low. EF significantly reduced after ECMO and was 33.012.5

(%) on ECMO day 5 without or minimum dose vasopressors.

4.2.2. The improvement of arterial blood gas

Before ECMO, because of severe cardiogenic shock arterial

blood gas was severe metabolic acidosis with pH 7.30.14, PaCO2

32.614.3 mmHg và HCO3 16.14.88 mmol/l, the metabolic acidosis sharply improved from ECMO day 2.

4.2.3. The improvement of organ function

In this study, Having been 7.82.68 before ECMO, SOFA

score did not change sifnificantly during ECMO, even slightly

increased because of the two things, the first if the patients had

acute kidney injury, they need severe weeks for recovering, the

second before ECMO the patient’s platelet was 19271.2 G/l,

after ECMO support, the platelet was 11146.0 G/l on ECMO day

2 and 8943.3G/l on stopped ECMO day, however after one day

20

SOFA score rapidly declined with mean 4.52.31 owing to

improved cardiovascular and coagulation score

4.3.1. Some prognostic factors of mortality

The survival rate was 82.14%, it was higher than the other

author’s rate. The high survival rate showed that the recovery of

myocardium in the group of acute myocarditis is higher than the

other causes’s recovery.

In our study, before ECMO there were 11 cardiac arrest patients

in the survival group and 7 in the non survival group, the cardiac

arrest associated with mortality rate in the non survival group was

nearly 70% and the mortality rate in cardiac arrest patients was 7.14

times as many as the mortality rate in non-cardiac arrest patients

Pulse pressure associated with mortality rate on day 5, the

mortality of patients having pulse pressure less than 20 mmHg on

ECMO day 5 was 12.5 times higher than patients having pulse

pressure greater than 20 mmHg (CI 95%, p=0.008). Pulse pressure

was related to the myocardium recovery, the lower pulse pressure,

the more severe heart function.

The study revealed that mean SAVE score was 2.5±4.37,

The prediction of mortality of SAVE score was higher than

prediction of mortality of APACHE II score, serum lactate

concentration and SOFA score. SAVE score with cut-off point -8

having sensitivity 87%, specificity 90% and AUC 0.69 for mortality

prediction.

4.3.2. Some complications of VA-ECMO

4.3.2.1. Bleeding complications

In this study, the ECMO cannula bleeding complication on

ECMO day 2, day 4 and on stopped ECMO day were 37%, 61.5%

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and 51.8% respectively. The lower rate of bleeding complication was

arterial line site that was 18.5% on ECMO day 2 and 46.2% on

stopped ECMO day, while the lowest rate was central line site,

12.5% on ECMO day 5. It was explained that the size of ECMO

cannula which was 16 F was much bigger than arterial line and

central line’s sizes, moreover the pressure of femoral artery was

very high that was the reason make not only higher bleeding

complication rate but also more severe bleeding quantity in ECMO

cannula site.

4.3.2.2. Lower limb arterial thrombosis complication

In our study, No severe lower limb arterial thrombosis

complication during ECMO that need intervention, however 5 cases

whom had lower limb arterial thrombosis after stopped ECMO by

ultrasound was treated by anticoagulant agents. During stopped

ECMO, 12 patients (21.2%) found lower limb arterial thrombosis

and it was removed by cardiac surgeon.

4.3.2.3. Acute pulmonary edema and neurologic complications

16 patients (29.6%) had acute pulmonary edema found by

clinical signs such as bloody frothy sputum through out endotube, it

may be involve left ventricle distension because during VA ECMO,

the arterial outflow cannula generates retrograde flow towards the

AV, resulting in higher afterload and increased left ventricular end

diastolic pressure. For markedly decreased ejection fraction patients,

VA-ECMO can cause increased left ventricle wall tension and

myocardial oxygen demand that made more severe acute pulmonary

edema and more severe outcome.

In our study, only 1 patient had cerebral infraction, however it is

certain that 44 survival patients (81.5%) without sneurologic

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sequelae so we can completely ruled out neurologic in these patients.

The remaining 9 death patients, we could not rule out whether the

patient had a neurologic complications event or not because of

patient's severe condition that did not allow performed brain CT

scan.

CONCLUSION

With 54 VA-ECMO supported acute myocarditis patients,

our study showed that:

1/ The improvements of circulation, arterial blood gas, organ

function

VA-ECMO helped improve circulation parameters, arterial

blood gas, organ function in acute myocarditis patients.

- The improvements of circulation

+ VA-ECMO helped increased mean arterial pressure,

decreased heart rate and inotropic equivalent index. Pulse pressure

was enormous fallen after ECMO support and returned significantly

on stopped ECMO day (p<0.05).

+ The serum lactate concentration significantly decreased after

ECMO with the it’s median before ECMO support and stopped

ECMO day were 7.55 mmol/l, 1.35 mmol/l respectively (p<0.05).

+ There was a significant drop Troponin T from ECMO day 3,

the median of Troponin T before ECMO, on day 3, on stopped

ECMO day were 4409.0 (U/L), 2320.0 (U/L) and 259.0 (U/L)

(p<0.05)

+ EF profoundly decreased from 34.4 ± 13.92% to 22.0 ±

6.67% (p<0.05) and it’s mean significantly increased to 47.7± 3.91%

on stopped ECMO day.

- The improvement of arterial blood gas: Metabolic acidosis was

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tremendous improved after ECMO, pH before ECMO and stopped

ECMO day were 7.300.14 and 7.440.12 respectively (p<0.05).

- The improvement of organ function: SOFA score did not go down

during VA-ECMO, 7.82.68 before ECMO and 9.9 ± 3.26 on stopped

ECMO day but profoundly decreased after stopped ECMO one day

4.52.31 (p<0.05).

2. Some prognostic factors of mortality and complications of VA-

ECMO

- Some prognostic factors of mortality

+ The survival rate was 82.14%

+ The mortality rate in cardiac arrest patients before ECMO was

7.14 times as many as the mortality rate in non-cardiac arrest patients

(OR 7.14, CI 0.03-0.65)

+ The mortality of patients having pulse pressure less than 20 mmHg

on ECMO day 5 was 12.5 times higher than patients having pulse

pressure greater than 20 mmHg (OR 12.5, CI 95%, p=0.008).

+ SAVE score with cut-off point -8 having sensitivity 87%, specificity

90 % and AUC 0.934 for mortality prediction.

- Some complications of VA-ECMO

+ The most bleeding complications were ECMO cannula site and

arterial line site, the highest bleeding rate on ECMO day 4 and on

stopped ECMO day were 33 cases (61.1%) , 25 cases (46.5%)

respectively.

+ Lower limb arterial thrombosis complication found 22.2% cases

during stopped ECMO

+ The rate of patients having DIC score greater than 5 was 18.5% on

before ECMO, highest rate 55.6% on ECMO discontinuation day

and significantly decreased 9.5% 24 hours later (p<0,05)

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+ ECMO cannula site infection: 16.1%

+ Acute kidney injury: 42.5%

PROPOSALS

1. VA-ECMO should be appied for acute myocarditis patients

complicated cardiogenic shock, life threatening arryhythmias and

carefully considered in cardiac arrest patients

2. Monitong coagulation tests by using ACT, ROTEM to

titrate quickly anticoagulant agents dose and treat coagulation

disorders, bleeding.

LIST OF PUBLISHED ARTICLE RELATING TO THESIS

1. Bui Van Cuong , Le Thi Viet Hoa, Dao Xuan Co (2020), “the

assessment of clinical outcomes of veno- arterial extracorporeal

membrane oxygenation in adult patients with cardiogenic shock

due to acute myocarditis”, Jounal of 108 – Clinical Medicine

and Pharmacy, (15), pp. 42-47.

2. Bui Van Cuong, Le Thi Viet Hoa, Dao Xuan Co (2020), “some

complications of veno- arterial extracorporeal membrane

oxygenation in cardiogenic shock patients due to acute

myocarditis”, Jounal of 108 – Clinical Medicine and Pharmacy,

(15), pp. 31-37.