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ORIGINAL ARTICLE
Year : 2021  |  Volume : 3  |  Issue : 1  |  Page : 18

Application of Awake Extracorporeal Membrane Oxygenation in Pediatric Acute Fulminant Myocarditis: A Single-Center Experience


1 Department of Pediatric Intensive Care Unit, Faculty of Pediatrics, Chinese PLA General Hospital, Beijing; Department of Pediatric Intensive Care Unit, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
2 Department of Pediatric Intensive Care Unit, Luoyang Maternal and Child Health Hospital, Luoyang, China
3 Department of Pediatric Intensive Care Unit, Faculty of Pediatrics, Chinese PLA General Hospital, Beijing, China

Date of Submission07-Sep-2021
Date of Acceptance08-Nov-2021
Date of Web Publication15-Dec-2021

Correspondence Address:
Prof. Xiaoyang Hong
Department of Pediatric Intensive Care Unit, The Second School of Clinical Medicine, Southern Medical University, Guangzhou
China
Prof. Zhichun Feng
Department of Pediatric Intensive Care Unit, Faculty of Pediatrics, Chinese PLA General Hospital, Beijing
China
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DOI: 10.4103/jtccm.jtccm_30_21

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  Abstract 


Background: Extracorporeal membrane oxygenation (ECMO) has been used for treating myocarditis for years. To extubate and be awake have been proven to be useful in adult patients supported with ECMO, especially for long-term pulmonary support. However, the role of awake ECMO remains still unclear in pediatric patients with acute fulminant myocarditis (AFM). Objectives: The objective is to summarize the application of awake ECMO during the treatment of pediatric AFM. Methods: Seven patients with AFM received ECMO from October 2018 to March 2020 in the Pediatric Intensive Care Unit, Senior Department of Pediatrics, the Seventh Medical Center of PLA General Hospital. During the process, the patients were extubated and supported with awake ECMO. Retrospective analysis of basic characteristics, clinical vital signs, outcomes, and parameters of ECMO was carried out. Results: All the patients received venoarterial mode ECMO during the treatment, and awake ECMO was implemented after the patients were stable. During the period, all the patients were fed with enteral nutrition. The respiratory and circulatory conditions were improved during the awake ECMO. Finally, all the patients successfully weaned from ECMO and survived to discharge from hospital. Conclusion: It is possible for pediatric ECMO-supported patients with AFM to extubation and keep awake. The choice of patients, close monitoring during process, and good coordination are key factors for the successful implementation of awake ECMO.

Keywords: Acute fulminant myocarditis, awake extracorporeal membrane oxygenation, pediatric patients


How to cite this article:
Zhao Z, Li L, Liu Y, Yang B, Zhang H, Hong X, Feng Z. Application of Awake Extracorporeal Membrane Oxygenation in Pediatric Acute Fulminant Myocarditis: A Single-Center Experience. J Transl Crit Care Med 2021;3:18

How to cite this URL:
Zhao Z, Li L, Liu Y, Yang B, Zhang H, Hong X, Feng Z. Application of Awake Extracorporeal Membrane Oxygenation in Pediatric Acute Fulminant Myocarditis: A Single-Center Experience. J Transl Crit Care Med [serial online] 2021 [cited 2022 Jan 21];3:18. Available from: http://www.tccmjournal.com/text.asp?2021/3/1/18/332522

Zhe Zhao, Lele Li; These authors contributed equally to this work





  Introduction Top


Extracorporeal membrane oxygen (ECMO) is a technique to drain venous blood from body and pump it back after the blood was oxygenated through a membrane oxygenator to maintain the oxygen delivery to the organism. ECMO could support cardiac and/or respiratory function temporally for a patient with cardiac and/or respiratory failure, in order for clinicians to treat the primary disease. Acute fulminant myocarditis (AFM) is often associated with an aggressive course and high risk of circulatory collapse. Patients with AFM typically suffer with rapidly progressive circulatory failure, cardiac shock, ventricular fibrillation, or even sudden cardiac arrest, which would need mechanical circulatory support such as ECMO.[1] According to the data from the Extracorporeal Life Support Organization (ELSO) Registry in 2021, the overall survival rate of pediatric patients with myocarditis was 83%.[2] Awake ECMO is a technique which allows patients under ECMO without intubation and be conscious.[3] During the period of ECMO, the patients, especially the pediatric patients, always need a large dose of sedation and analgesia or even need to be paralyzed.[4] All these agents were proven to be strongly correlated with delirium, which was associated with prolonged hospital stay and poor prognosis.[5] Adult patients with awake ECMO were reported in recent years, and most cases were used for respiratory support or waiting for lung transplant.[6] The reports of pediatric awake ECMO cases were rare, especially for pediatric patients with AFM. Thus, in this report, we analyze/present seven cases suffered from AFM who were treated with awake ECMO from December 2018 to March 2020.


  Methods Top


We collected clinical data of patients treated with ECMO in the Pediatric Intensive Care Unit (PICU) of the Seventh Medical Center of PLA General Hospital from October 2018 to March 2020. All the patients were diagnosed with AFM in accordance with the following criteria.[7] The first main clinical diagnostic basis included: (1) cardiac function failure, cardiac shock, or cardiocerebral syndrome; (2) cardiac dilatation; (3) elevation of plasmic cardiac troponin T or cardiac troponin I or creatine kinase-MB and dynamic alteration; (4) obvious alteration of electrocardiogram (ECG); (5) typical clinical magnifications on cardiac magnetic resonance. The secondary clinical diagnostic basis included: (1) a prior infection history, such as a history of upper respiratory or gastrointestinal viral infection within 1–3 weeks before onset; (2) at least two symptoms such as chest tightness, chest pain, palpitations, fatigue, dizziness, pale face, gray face, and abdominal pain, and small baby may have breast rejection, cyanosis, cold limbs, etc.; (3) elevation of plasmic lactate dehydrogenase, α-hydroxybutyric dehydrogenase, or aspartate transferase; (4) a mild abnormal change of ECG; (5) the anti-myocardium antibody shows positive. When the patients got with more than three main criteria or with two main criteria and more than three secondary criteria and other diagnoses were excluded, they could be diagnosed with myocarditis clinically. When the patients diagnosed with myocarditis had rapidly progressed severe cardiac or circulatory disorders, they could be diagnosed with AFM. The protocol was approved by the Ethics Committee of the Seventh Medical Center of PLA General Hospital (previously known as PLA Army General Hospital, No. 2018-15).

The indications of ECMO for patients with AFM are as follows:[7] (1) the patient was diagnosed with AFM definitely; (2) cardiac index (CI) <2 L/m2/min or left ventricular ejection fraction (LVEF) <40%–45%, or fractional shortening (FS) <26%; (3) persistent low tissue perfusion; (4) persistent hypotension; (5) hypotension with two or more vasoactive inotropic agents or the vasoactive inotropic score (VIS) ≥40 and elevated progressively; (6) severe arrhythmias such as ventricular fibrillation, cardiac arrest or pulseless electrical activity, short ventricular tachycardia, grade III atrioventricular block without a stable circulation state through antiarrhythmic drugs, positive inotropic drugs, or temporary cardiac pacemakers; and (7) routine cardiopulmonary resuscitation (CPR) for over 15 min without a stable circulatory state.[8] The patients would be supported on ECMO under the condition 2~6 for over 3 h.

The exclusion criteria were as follows:[7] (1) severe brain dysfunction or confirmed brain death; (2) severe metabolic acidosis: lactate over 10 mmol/L for over 10 h; (3) severe multiple organ dysfunction for a long duration, such as renal failure, with urine <0.5mL/(kg·h) or anuria for 10 hours, or liver failure, with prothrombin time activity (PTA) ≤20%, or international normalized ratio (INR) ≥2.6 or prothrombin time (PT) >36s for over 10 hours.

Application of venoarterial extracorporeal membrane oxygenation

The right jugular vein and right common carotid artery (RCCA) were cut and catheter was inserted by the surgeons for venoarterial (VA) ECMO support for patients less than 30 kg. However, the femoral vein and artery were used for catheter through puncture for those patients above 30 kg, and the distal perfusion tube was inserted once the ECMO was initiated. Centrifugal pumps (Bio-Console 560, Medtronic, USA; DataStream DP3, Medos, Germany; SCPC, Sorin, Italy) were used with the flow differing from 94.11 to 128.89 mL/kg/min in all the patients. During the process, the gas flow of the oxygenator was modulated according to the analysis of blood gas, and the gas-to-blood ratio was from 0.5:1 to 10:1. The oxygenators (Hilite 2800/7000, Medos; Lilliput, Sorin, Italy) were selected according to the body weight of the patient to get blood flow of 150 mL/kg. Heparin was used for anticoagulation to maintain activated clotting time between 180 and 220 s.

Application of awake extracorporeal membrane oxygenation

The indications of awake ECMO in our center were as follows: (1) the circulatory state was stable under ECMO; (2) evaluated by cardiac ECHO, open of the aortic valve was not restricted or mild mitral regurgitation; and (3) clear chest X-ray without obvious exudation. The spontaneous breath test of the patients was successful and no respiratory distress was observed for 4 h; (4) the parameters of mechanical ventilation was as follows: Ppeak <16 cmH2O, PEEP ≤5 cmH2O, and FiO2 <0.45; (5) the patient could be awake without any symptoms of nervous system injury; and (6) ECMO system runs well without any severe mechanical complications. If the patient fulfilled the criteria, sedation agents would be decreased gradually. The oral trachea cannula would be taken out and the patient would be supported with other mode of oxygenation.

The awake ECMO would be considered failed if the following situations happened. The circulatory state of the patient cannot be stable, such as the drop of arterial blood pressure was beyond 20%, the decreased LVEF or FS, persistent low perfusion of tissue, and the elevated support of vasoactive inotropic agents. Progressively worsening dyspnea, severe hypoxemia, or retention of carbon dioxide means that the patient was not suitable for extubation. The patient could not clear the secretion, and the airway was blocked severely. When the patient showed progressive appearance of consciousness disorders or the chest radiograph showed progressive enlargement of lung infiltration, the awake ECMO was failed. Once the situation occurred, the patient needed to be sedated and re-incubated immediately.

During the period of awake ECMO, the patients could be accompanied by their parents who had received aseptic technique education, for 2 h per day to keep the patients calm. During the daytime, the patients would be accompanied by the nurses and play games on electronic devices or read books of their choice. At the same time, the patients would participate in rehabilitation programs and do some respiratory exercises such as cough.

Data collection and statistics

Basic characteristic demographical information and information of the patients before ECMO were collected in our study [Table 1]. The data associated with the patients were as follows: age, gender, height, body weight, body surface area, body mass index, underlying diseases, VIS, and pediatric critical illness score (PCIS) at administration.
Table 1: Characteristics of patients at the beginning of extracorporeal membrane oxygenation, median (interquartile range)

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The data about ECMO were extracorporeal CPR or not, ECMO mode, cannulation position, type of catheter, left atrium decompression or not, the mode and position of left atrium decompression, and duration of ECMO. Duration of awake ECMO, the ventilation mode during the awake ECMO, dosage and duration of sedation and analgesia, and complications around awake ECMO were also recorded. The delirium state was measured with the Cornell assessment of pediatric delirium (CAPD), which was recommended by the European Society of Pediatric and Neonatal Intensive Care in 2016.[9] Chinese version of CAPD consists of the evaluation master table and the reference schedule. The table was mainly assessed at 9:00 am every morning during ECMO by the clinical staff with five items/parameters, i.e., “never”, “rarely”, “sometimes”, “often”, “always”. The Likert 5-level scoring method is used to calculate the final score. The patient would be assessed as delirium when the score reached 9.

The primary outcomes were survival rate and possibility of ECMO weaning. The secondary outcomes included the dosage and duration of sedation agents, running time of ECMO, time of intubated mechanical ventilation (MV), and PICU time.

The statistical analysis was performed with SPSS 24.0 (SPSS Inc., Chicago, USA). The continuous variables are shown as mean ± standard deviation or median and interquartile range. Frequency and percentage were used for category variables. The characteristics and outcomes of each pair were compared based on the exact sign tests and 95% confidence intervals for the median and estimation.


  Results Top


Characteristics of the patients

From October 2018 to March 2020, seven children diagnosed with AFM have received awake ECMO support [Table 1]. There were three males and four females, with a median age of 10 (1–12) years. The median VIS score before ECMO was 40 (36.5-50.5), and the median PCIS score before ECMO was 73 (66, 79). All cases were eventually discharged.

Clinical application during awake extracorporeal membrane oxygenation

During cannulation, all the patients were with invasive MV (IMV), sedation, and analgesia and paralyzed. All the patients were supported with VA mode. Among them, four cases cannulated through right internal jugular vein and RCCA and three cases through femoral vein and femoral artery (drainage tube of 14–19 Fr and perfusion tube of 10–17 Fr). A 5 Fr distal perfusion tube was inserted into the femoral artery for patients supported through femoral artery. In our reports, the median IMV time was 96 (48, 104) h and the total ECMO run time was 163 (146, 179.5) h. The duration of awake ECMO was 100 (61, 108) h. The overall PICU stay time of the patients was 13 (10, 35) days. Compared with the status during ECMO with IMV, the indicators such as the heart rate, blood pressure, fluid intake and output, circulatory status, and the application of vasoactive agents changed, while without any statistical significance [Table 2].
Table 2: Characteristics of patients before and 24 h after awake extracorporeal membrane oxygenation, mean±standard deviation

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Evaluation of neurological conditions of the patients

The CAPD score after awake ECMO in the first 24 h was 8 ± 0.82. The score in the second 24 h after awake ECMO was 7.29 ± 0.49. The above data showed that after removing the oral intubation and stopping sedation, the consciousness level of the children improved. At the same time, the limb function exercise could be carried out under guidance, which was beneficial to the recovery and evaluation of the nervous system.

In this report, the survival rate of all patients was 100%, and the ECMO withdrawal rate was 100% [Table 3]. One patient was re-intubated 3 days after extubation because of tachycardia and pneumothorax. The other two patients were intubated again 2 days and 3 days after extubation, respectively, because of withdrawal of ECMO.
Table 3: Outcomes of patients with awake extracorporeal membrane oxygenation

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Complications

In all the cases of this study, during the operation of ECMO, the main complications related to ECMO were bleeding (42.9%), liver function damage (28.6%), renal function damage (14.3%), and pneumothorax (14.3%). The complication related to ventilator was pneumothorax (14.3%). The above complications occurred before awake ECMO.


  Discussion Top


According to the recommendations from ELSO, sedation, analgesia, and MV play important roles in the treatment during ECMO. However, the complications are also associated with the progress and prognosis of the disease.[10] As the ECMO technology and understanding of the complications during MV develop, medical centers around the world have tried to use awake ECMO for patients with different diseases.[6],[11],[12] During the period of awake ECMO, less sedation agents and less time of MV had been used,[13] which means that it could be easier to observe and manage the complications during the treatment. We retrospectively analyzed seven cases of awake ECMO in our center and found that the use of awake ECMO decreased the duration of sedation and associated complications or which was valuable for the observation of neurological complications during the after being extubated.

Influence to the respiratory system

Ventilator-associated pneumonia (VAP) has been proved to be the primary complication for patients with IMV.[14] Among patients who have received MV for over 5 days, 77% of them would suffer from at least one kind of complications associated with ventilator and 29% would get infectious respiratory complications.[15] Intubation may cause injury of the respiratory mucosa and cilium of upper respiratory tract, which could increase the risk of VAP. Besides, the use of sedation, analgesia, and even neuromuscular blocker could further decrease the movement of cilium for patients receiving MV. Diaphragm could also be affected during this period because of the negative movement and positive pressure of MV, which would lead to abnormal V/Q ratio. During the period of awake ECMO, the patient could cough positively, which is better for sputum excretion. The risk of aspiration and associated aspirated pneumonia also decreased due to the downregulation of sedative agents. During awake ECMO, six patients received nasal oxygen and one with continuous positive airway pressure (CPAP) ventilation. The patient who was only 1 year old was too young, so he/she needed CPAP after extubation. The oxygenator could keep partial pressure of CO2 physically, which did not cause the increase of the respiratory rate during awake ECMO. According to the mentioned data, awake ECMO would not increase work of breath and decrease the respiratory complications associated with sedation and paralysis.

Influence to the circulatory system

The core function of ECMO is to supply enough oxygen delivery. Meanwhile, to drain the venous blood from right atrium could decrease the preload of right ventricle. Sedation and analgesia are necessary at the beginning of cannulation since most cannulation would require surgery. However, the positive pressure during mechanical ventilation, especially PEEP, would increase the postload of the right ventricle, which could delay the recovery of the pump function of the heart. Moreover, the circulatory complications associated with sedative agents, such as midazolam and fentanyl, are major concerns for patients supported with ECMO.[15] Along with the withdraw of sedative agents, autonomous respiration allowed negative pressure of pleural cavity during inspiration, which would be better for the venous return. In this case series, the circulatory function did not show obvious change before and after extubation. After extubation, the patient did not need a higher ECMO flow or gas escape, as well as higher the vasoactive or inotropic agents. The heart rate, blood pressure, mean blood pressure, and level of lactate 24 h before and after extubation did not show significant alterations [Table 2]. The EF and CI in the echo test showed no obvious change. During support with stable ECMO, awake ECMO could be trialed without any circulatory complications for patients who had been evaluated properly.

Cerebral aspects related to awake extracorporeal membrane oxygenation

Delirium in children is a state of acute brain dysfunction, which occurs frequently in PICU.[16] Delirium is more likely to occur among patients less than 2 years old who received IMV, vasoactive drugs, and anticonvulsant drugs. The risk is higher if the patients received limb restraint, analgesia, sedation, and steroids.[17] The appearance of delirium is not conducive to the stability of the autonomic nervous system nor the recovery of primary diseases. The risks of unplanned extubation and falling from the bed were increased and the admission time would be prolonged.[18] The increase of 6-month mortality and medical costs was also proven to be associated with delirium.[9] Therefore, early identification of delirium in critically-ill children and timely intervention, such as the removal of related factors leading to delirium, could be useful for patients in PICU.

A central issue in conventional ECMO transport is the complication of analgesic sedation and IMV since/because it can result in disease progression and poor outcomes.[10] Studies suggest that there is a strong correlation between the use of analgesic sedative drugs and delirium. A 1-day point prevalence international study showed that the use of invasive devices and sedatives was the main modifiable risk factor of delirium. Patients with delirium had a greater severity of illness at admission, increased ICU, and hospital mortality as well as longer hospital length of stay. In addition, mounting/increasing evidence demonstrated that delirium is associated with the risk of self-extubation, removal of catheters as well as emotional awareness disorders, which are not conducive to hemodynamic stability and clinical medical safety.[19] There is an urgent need to address the safety problems caused by delirium. Recently, researchers have become increasingly interested in awake ECMO, a choice for support with ECMO implanted in conscious patients who need less sedatives, therefore reducing the occurrence of delirium. Removing the interference of sedatives, awake ECMO can accurately evaluate the central nervous system to guide clinical intervention and prognosis assessment. Another advantage is that older children can carry out early limb functional exercise to reduce the incidence of ICU-acquired myopathy[20] and pressure sores caused by long-term bed rest. Moreover, sober children can express accurately and receive humanistic psychological intervention, which could better ensure emotional stability and comfort. In this study, we observed that all the seven children survived without ECMO complications. Thus, awake ECMO can not only ensure the satisfactory oxygenation and stable hemodynamics but also is particularly good for the recovery of consciousness and emotional psychology of the patients.[19]


  Conclusion Top


Awake ECMO could be applied for pediatric patients with AFM after proper evaluation, which has been proved to be a safe and effective way of treatment. However, this report was only a single-center case series and the sample size was small. More cases and multicenter research are needed for the further study of the efficiency and safety of awake ECMO.

Financial support and sponsorship

This present study was supported by Capital's Funds for Health Improvement and Research (grant No. 2020-2-5093) and Key Logistics Research Projects of Chinese PLA (grant No. BLJ18J006).

Conflicts of interest

There are no conflicts of interest.



 
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