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Research Proposal
Mechanical Ventilation using CCSV combined with ABO improves resuscitation
outcome and alleviated multiple organs injury following long-term cardiac arrest
resuscitation in a porcine Model
Ph.D. Emergency Medicine
Zhejiang University
Dr. Zafar Ullah Khan
Supervisor : Professor Zhang Mao
Table of Contents
Introduction....................................................................................................................3
Aim and Objectives....................................................................................................6
Methodology..................................................................................................................6
Establishment of animal model..................................................................................6
Animal randomized grouping and intervention .........................................................6
Parameters setting:.........................................................................................................7
Observation indicators: ..................................................................................................7
Expected outcome..........................................................................................................8
Results........................................................................................................................8
Discussion..................................................................................................................8
Conclusion ...................................................................................................................11
References....................................................................................................................13
Introduction
Background
Cardiac arrest (CA), which has a high incidence rate and a high mortality rate, has
become one of the major issues of public health worldwide. The data from the Europe
and USA has manifested that the initial rates of resuscitation success in non-traumatic
and traumatic CA (Cardiac arrest) victims were 40% and 15.4%, and their survival to
hospital discharge were 10.4% and 5.1%, respectively. The clinical prognosis of CA
victims is still worse in developing countries. Striving to improve the level of clinical
treatment of CA has become a major challenge in the field of resuscitation. Clinically,
after the CA incident, the treatment mainly includes cardiopulmonary resuscitation
(CPR). CPR stage basic life support and post resuscitation organ protection strategy. In
recent years with the continuous improvement and enhancement of pre hospital
emergency service system, the continuous progress and popularization of CPR
technique, and the ability and willingness of the public to participate in resuscitation
and treatment were improved simultaneously, and CA patients achieved self-circulation
at CPR stage. The ratio of Return of spontaneous circulation (ROSC) has significantly
increased. It has been suggested that after experiencing one CA event, the key factors
for improving the outcomes of CA victims are to effectively improve the techniques of
basic life support during cardiopulmonary resuscitation (CPR) and also enhance the
degree of organ protection during the post-CPR care.
The aim of cardiopulmonary resuscitation (CPR) is to give the cardiac arrest patient the
best chance of achieving a return of spontaneous circulation and survival. At present,
the American Heart Association (AHA) and European Cardiopulmonary Resuscitation
Council (ECR) update their guidelines on CPR every five years. CPR, as the main
treatment for sudden cardiac arrest, includes circulation, airway, breathing, and
defibrillation, each of which is important for overall success. However, there are many
controversies about when to establish an advanced airway, which ventilation method to
choose and how best to set ventilator parameters.
At present, there are no recommendations for the best mechanical ventilation strategy
during CPR. The most common settings are: VC mode, tidal volume of 6–7 mL/kg,
PEEP of 0–5 cmH2O, rate of 10/minute, and 100% oxygen, while turning off inspiratory
triggers or adjusting the pressure trigger level to 20 cmH2O or above, and having a high-
pressure alarm set to 50 cmH2O. However, the best ventilation modes are still being
explored, including pressure-controlled ventilation (PCV), chest compression
synchronous ventilation (CCSV), continuous positive airway pressure/pressure support
ventilation (CPAP/PSV), and ultra-low tidal volume ventilation.
Our survey found that there are a variety of ventilator parameter settings used in
Chinese tertiary hospitals. From what mode to use, to Vt, PEEP or FiO2, only the
respiratory frequency setting was consistent. The effect of thoracic pressure on
hemodynamics and survival rate in patients with CPR is still controversial, and even if
hypoxemia has an impact on the survival rate, experimental results are not consistent.
findings showed that ventilator parameter settings for CPR patients are very variable,
and the relevant ventilation recommendations in the guidelines are not very specific.
There are many factors that need to be considered for proper ventilator settings: patient
size and weight, comorbidities, the cause(s) of cardiac arrest and so on. But it is worth
mentioning that more than half of surveyed physicians still report mistriggers and high-
pressure alarms. Mistriggers often means higher respiratory frequencies are given.
High-pressure alarms mean that lower tidal volumes are being delivered. This most
likely is due to trigger pressures and high-pressure alarms for ventilators not being
effectively adjusted during resuscitation. This aspect of ventilator training is should be
a productive area for added emphasis.
In this research we will focus on new technique of ventilation during CPR i-e CCSV
combine with ABO during CPR to improve outcome and decrease post resuscitation
organ damage .
Chest Compression Synchronized Ventilation (CCSV) mode of ventilation has
originated from WEIMANN Emergency which has been found to be revolutionizing
during the process of resuscitation. During this process of chest compression,
pulmonary vessels and heart are compressed which don’t allows the volume of gas to
escape from the lungs and provides support during chest compression (Kill et al.). In
comparison to IPPV and BiLevel, CCSV works best with the preset ventilation values
without exceeding the preset ventilation pressure during simulated resuscitation. Both
the compression depth and the compression frequency were similar during the
application of the different ventilation modes. This demonstrated that none of the
examined ventilation patterns had a negative impact on the quality of the chest
compressions.
In the course of resuscitation, CCSV may be considered as an effective ventilation
mode. In some animal studies, compared with traditional positive pressure ventilation,
this new ventilation mode improves gas exchange, enhances hemodynamics and
increases tissue oxygenation Compared with IPPV, in the pig model of cardiac arrest,
all CCSV modes lead to higher PaO2 and prevent the decrease of arterial blood pressure
during resuscitation (Kill et al.).
Therefore, with CCSV the disadvantages of conventional ventilation during
cardiopulmonary resuscitation can be prevented and the gas exchange and
hemodynamics can be improved demonstrably.
ABO (Aortic Balloon Occlusion) has been found to facilitate the success of CPR which
has resulted in the cardiac arrest which is effective in controlling the traumatic
hemorrhage (Daley et al.). This process has been investigated in various studying which
discussed the effects of ABO on resuscitation outcomes and the duration of post-
resuscitation of organ protection in a porcine model associated with TCA (traumatic
cardiac arrest). REBOA is used as an adjunct in traumatic or nontraumatic CPR, it might
be of importance to carefully determine the aortic occlusion level prior to inflation of
the balloon. REBOA in cardiac arrest seems to be a promising therapeutic intervention
to be investigated in humans, as a primary intervention to achieve ROSC or as a bridge
to more definitive care like percutaneous coronary intervention or/and extracorporeal
membrane oxygenation. However, the optimal use of REBOA must be further explored
in randomized studies. Studies are necessary to determine the effects of continuous
aortic occlusion during CPR on hemodynamics, ROSC, long term survival and
neurologic outcome. Furthermore, the optimal duration and adverse effects of intra-
arrest REBOA implementation remains unknown.
The combination of ABO+CCSV in order to recover the pigs from cardiac arrest was
very much effective because of their synergistic effects.
Research Design:
Research design can be defined as the framework of research methods and techniques
that can be chosen by a researcher in order to design a methodology for the research
study. The design used in this research study is experimental. Experimental research
design has been found to be centrally concerned with the data constructing the research
which is associated with high causal and internal validity. This research study will use
a randomized control trial in which there will be two groups of population (pig models).
These groups will be named as the experimental group and an intervention group. The
experimental group will be treated with both ABO and CCSV in order to check the
resuscitation of long-term cardiac arrest in the pig models. The intervention group will
be treated with either ABO, CCSV or IPPV in order to create a comparison with the
experimental group. This research design has been selected for this research study
because of the fact that it has been used in various other research studies (Auinger et
al.). In a similar research study written by Xu et al. it can be said that there is an
enhancement in the success rate of cardiopulmonary resuscitation in cardiac arrest when
ABO is used. This paper found that post-resuscitation cardiac, neurological dysfunction
and other organ damages were milder for the experimental group than the control group
which did not use the intervention (ABO). ABO has been found to be augmented
associated with the efficacy of CPR after TCA and improved post-resuscitation cardiac
and neurological outcomes were observed. Thus, it can be stated that the combination
with CCSV will be beneficial for the enhancement of the resuscitation process and
protection of organs from damages. This is the overall research design of this research
study since it is based on a similar topic.
Aim and Objectives
The main aim of this study is
Chapter 1. To understand the effect of CCSV +ABO on CPR outcome after
long-term CA using experimental Porcine model.
Chapter 2. To evaluate the effect of CCSV combined with ABO on multiple
organs injury and short-term survival prognosis following long-term cardiac
arrest resuscitation in a porcine model.
Methodology
Establishment of animal model
All animals were prepared for general anaesthesia. General anaesthesia was started by
Ketamine injected intramuscular at dose of 20mg/kg and completed by venous injection
of 2 mg/kg propofol. ETT (endotracheal tube) was introduced into the trachea. Later
General anaesthesia was maintained by intravenous infusion of propofol at dosage of 4
mg/kg.h and fentanyl at 2mg/kg.h.
Ventricular fibrillation (VF) was induced with a right ventricular paced electrode and
AC 7.5 to 15V. VF remained untreated for 8 minutes without any ventilation or chest
compression. Lucas cardiopulmonary resuscitation instrument was used for continuous
chest compression. With the beginning of chest compression at = 8 min, mechanical
ventilation was performed for five periods of eight minutes each. Weinman transport
ventilator was used to perform mechanical ventilation. 20 microgram/kilogram of
adrenaline was administered for 2 minutes of CPR and this process was repeated every
four minutes. Defibrillation was performed with 150 Joules of electrical energy once at
8 minutes CPR. When ROSC will not be restored, the CPR will be restarted
immediately every two minutes after defibrillation. This cycle is repeated every five
times until the resuscitation is successful or fails.
Monitor for 4 hours after successful resuscitation: 1) restart mechanical ventilation; 2)
continue anesthesia monitoring; 3) maintain normal body temperature at 38 ℃. 5.
Observation in pigsty for 20 h.
Animal randomized grouping and intervention
Experimental group
A total of 32 healthy male white pigs weighing approximately 35 kg were randomly
divided into 4 groups (group n=8/): 1) group IPPV (intermittent positive pressure
ventilation), 2) group CCSV (Chest Compression Synchronized Ventilation), 3)
group IPPV+ABO ( aortic balloon occlusion ) and 4) group CCSV+ABO.
1) IPPV group: IPPV ventilation mode was adopted during CPR, and ABO was not
implemented.
2) CCSV group: CCSV ventilation mode was adopted during CPR, and ABO was not
implemented.
3) IPPV+ABO group: IPPV ventilation mode was used and ABO were implemented
during CPR.
4) CCSV + ABO group: CCSV ventilation mode was used and ABO was implemented
during CPR.
Parameters setting:
1) IPPV mode before resuscitation: FiO2 21%, Vt 8 ml/kg, RR (determined by ETCO2),
I:E=1:2, PEEP 0 mm Hg, inspiratory peak pressure 60 mbar;
2) IPPV mode during resuscitation: FiO2 100%, Vt 7 ml/kg, RR 10 /min, I:E=1:2, PEEP
0 mm Hg, inspiratory peak pressure 60 mbar;
3) CCSV mode during resuscitation: FiO2 100%, inspiratory peak pressure 60 mbar,
time 265 ms;
4) ABO implementation during resuscitation: During the resuscitation, ABO was used
to block the blood flow completely by balloon inflation in the diaphragmatic region of
aortae zone I.
5) IPPV mode after resuscitation: FiO2 21%, Vt 8 ml/kg, RR (same as before
resuscitation), I:E=1:2, PEEP 3 mm Hg, inspiratory peak pressure 60 mbar.
Observation indicators:
Observation indicators during CPR
1. Brain indicators: real-time monitoring of cerebral oxygen saturation and carotid
blood flow, and use of ultrasound to evaluate cerebral perfusion and jugular
arteriovenous blood flow at 1 minute, 4 minutes, and 7 minutes of CPR;
2. Cardiac indicators: real-time monitoring of coronary perfusion pressure, and
evaluation of cardiac perfusion and large vessel blood flow using esophageal
ultrasound at 1 minute, 4 minutes, and 7 minutes of CPR;
3. Pulmonary indicators: real-time monitoring of ETCO2, Pulmonary electrical
impedance tomography.
4. Large circulation indicators: real-time monitoring of heart rate, MAP, RAP;
5. Microcirculation index: real-time observation of sublingual gland microcirculation;
6. Metabolic indicators: detect arterial blood gas (including pH, PO2, PCO2, BE,
lactate, etc.) at 4 and 7 minutes of CPR;
7. Record ROSC rate, resuscitation time, frequency of defibrillation and dosage of
adrenaline were recorded.
Observation indexes after resuscitation
1. Brain indexes: 1) blood samples were collected to detect NSE at 1 h, 2 h, 4 h and 24
h after resuscitation; 2) neurological function (CPC and NDS) were evaluated at 24 h
after resuscitation; 3) brain tissues were obtained to evaluate cell apoptosis (TUNEL,
caspase-3) at 24 h after resuscitation;
2. Cardiac index: 1) PiCCO was used to evaluate cardiac function at 1 h, 2 h and 4 h
after resuscitation; 2) cTnI was detected at 1 h, 2 h, 4 h and 24 h after resuscitation; 3)
myocardial tissue was obtained to evaluate cell apoptosis (TUNEL, caspase-3) at 24 h
after resuscitation.
3. Lung indicators: (1) at 1, 3, and 6 hours after resuscitation, PiCCO was used to
evaluate ELWI and PVPI; (2) at 1, 3, 6, and 24 hours after resuscitation, pulmonary
ultrasound score was used; 3) electrical impedance tomography (EIT);
3. Lung parameters: 1) at 15 min, 1 h, 2 h, 4 h after resuscitation, PiCCO was used to
evaluate ELWI and PVPI; (2) at 15 min, 1 h, 2 h, 4 h, 24 h after resuscitation,
pulmonary ultrasound score was performed; 3) at 15 min and 1 h after resuscitation,
pulmonary electrical impedance imaging indexes ( electrical impedance tomography
); were evaluated;
(4) Macrocirculation indicators: real time monitoring HR, MAP, RAP;
(5) Microcirculation indicators: real time observation of sublingual gland
microcirculation;
6. Metabolic index: arterial blood gas (including pH, PO2, pCO2, be, lactic acid, etc.)
was detected at 15 min, 2 h and 4 h after resuscitation;
7. Survival outcome: 4 h and 24 h survival rate;
8. Assessment of aortic injury: at 24 hours after resuscitation, aortic tissue from
balloon indwelling site was obtained for HE staining to observe the pathological
damage.
Expected outcome
Results
1. CCSV +ABO improves resuscitation outcome , shortened CPR time,
reduced the number of defibrillations, decreased the dosage of epinephrine
and significantly increased the ROSC rate.
2. CCSV + ABO significantly prevents organ damage because of the
synergistic effect of CCSV and ABO.
Discussion
Cardiac arrest is a condition associated with the sudden loss of blood flow which
results from a failure of heart which cannot pump blood effectively. The symptoms
have been found to include the loss of consciousness and abnormal breathing.
Sometimes a total absence of breathing is also associated with this disorder (Makhni et
al.). This process is also known as cardiopulmonary arrest which leads to the loss of
consciousness and partial to permanent death of an individual. The same condition has
been observed in pig models. The main causes of cardiac arrests are congenital heart
disease, cardiomyopathy, diseases associated with heart valves, acute myocarditis
which leads to the inflammation of heart muscle. Cardiac arrest has been observed as a
devastating event for many years in spite of improving resuscitation practices
associated with the mortality who suffer an OHCA (out of hospital cardiac arrest)
(Makhni et al). However, some of them has been found to make a good recovery and
return home with good life quality.
This is first study on CPR to compared the effects of mechanical ventilation by an
automated transport ventilator using a new ventilator mode for resuscitation CCSV and
ABO combine. Pigs are selected as experimental animals because their metabolism,
cardiovascular function and cardiac anatomy are very similar to those of human beings,
which has been considered as the best animal for human CPR research (Idr4). Secondly,
because ventricular fibrillation is the most common cause of clinical CA, this study
chose ventricular fibrillation to induce CA. Moreover, considering that most of the out
of hospital patients can only be cured after more than 8 minutes of CA, a stable and
feasible long-term CA model will be more conducive to the preliminary basic research
of clinical CPR. The animal model will be established by referring to the pig model
method in reference (XuJ2) and combining with the requirements of the latest CPR
guidelines in 2015 (Neu2).
Reviewing the existing clinical or animal studies on ventilation methods, in addition to
the contradiction between different experimental results, the difference between
different groups in the same experiment is not particularly significant. In addition to the
different research programs, for adult patients with cardiac arrest in CPR, compression
and defibrillation are in a higher priority than ventilation. This is because in some cases,
even without active ventilation, certain arterial oxygen content can be ensured (Tan5).
In the first few minutes of cardiac arrest, certain oxygen content can be maintained in
the heart and large blood vessels. When chest compressions are carried out soon after
cardiac arrest, the residual oxygen in the alveoli can be reduced in a short time It can
maintain oxygenation; after compression relaxation, the negative pressure produced by
chest rebound can produce passive ventilation; the common wheezing phenomenon in
cardiac arrest can also provide additional ventilation; even if the VT of passive
ventilation and wheezing produced by compression is lower than normal, it can
maintain the appropriate ventilation / blood flow ratio at a relatively low level compared
with the lung hypoperfusion during CPR. In addition, most studies choose short-term
cardiac arrest model, the body hypoxia is not very serious, the role of ventilation cannot
be reflected; and for some asphyxia cardiac arrest, long-term cardiac arrest model, the
role of ventilation is more reflected. Therefore, how to choose the best mechanical
ventilation strategy at the same time of CPR is still a problem worthy of further
discussion, and how to balance the relationship between compression and ventilation is
still the key to solve this problem. This research study deals with long term cardiac
arrest pig models in order to study the effect of novel resuscitating process CCSV and
Aortic balloon occlusion at a time. During the condition of CPR, coronary perfusion
pressure has been found to be very important for high resuscitation outcome. CPP was
significantly increased following a high resuscitation rate of success in the 30-60
minutes CCSV group that was compared with the control group (Kil). There are very
limited studies on the effect of CCSV on resuscitation outcome during non-traumatic
cardiac arrest animal model. The study conducted by kill et al (Kil4) shows that the
oxygenation and hemodynamics of CCSV model were better than IPPV and bilevel
model.A study by kill et al. shows CCSV provides Improved and better hemodynamics,
Mechanical ventilation provides favorable conditions for cardiopulmonary
resuscitation with safe airway. kill et al. Studied the effects of volume-controlled
ventilation (IPPV), bilayer ventilation (BiPAP) and new CCSV ventilation mode on gas
exchange and hemodynamics in pig model and found that CCSV mode had better
oxygenation and improved hemodynamics. (Kil4).
This research study deals with pig models in order to study the effect of two
resuscitating process at a time. Human beings have been found to experience chest pain,
nausea and shortness of breath before a sudden cardiac arrest. During the condition of
CPR, coronary perfusion pressure has been found to be significantly increased after
following a high resuscitation rate of success in the 30-60 minutes. CCSV group that
was compared with the control group (Kill et al). According to the observations, after
the resuscitation process of cardiac arrest, neurological problems and injuries were
found to be higher for the model pigs of the control group. A significant milder and less
intestinal and renal injuries were observed for the experimental group. The combination
of ABO+CCSV in order to recover the pigs from cardiac arrest was very much effective
because of their synergistic effects. These factors were measured after the collection of
blood gas samples which are drawn from each of the periods named as MAP (mean
arterial pressure) and CVP (central venous blood pressure). These two measurements
along with other parameters will be continuously recorded. A similar discussion was
made on a research paper discussing the same topic as this research study (Kill,
Clemens, et al). There are various advantages of using automatic chest compression
detections, uninterrupted chest compressions, can be used in mechanical compression
devices associated with chest, easier to integrate inside the standard resuscitation
procedures, has improved arterial pressure, improved gaseous exchange and also
improves the circulation of blood. According to various observations in CCSV mode,
a specific mechanical breath is initiated in synchronization with each of the
compressions made in the chest. Thus, no gas volume is allowed to escape from the
lungs and the lung pressure has been found to provide support to the chest compression
(Pietilä et al.). A device known as frequency tachometer has been found to maintain
an optimum compression frequency. There is a great advantage of CCSV which states
that the ventilation mode can also be used along with devices associated with
mechanical chest compressions. Resuscitative endovascular balloon occlusion of aorta
is a very significant topic of research on resuscitation since the last years (Pietilä et al.).
Resuscitative endovascular balloon occlusion of the aorta has been found to be
increasingly used in resuscitation of trauma victims all over the world. This process has
been reported to elevate blood pressure followed by limiting the infusion of fluid when
various other procedures are aimed at stopping the bleeding. The resuscitative
endovascular balloon has been occlusion of the aorta has been found to increase since
the last ten years.
Conclusion
Thus, after going through the study it can be stated that Chest Compression
Synchronized Ventilation (CCSV) mode of ventilation has been revolutionizing during
the process of resuscitation. In this pig model of cardiac arrest, compared with the non-
synchronous intermittent positive pressure ventilation with volume control, the
mechanical ventilation with external chest pressure synchronous ventilation can
improve the cooperation of arterial oxygen and better maintain arterial blood
pressure.ABO (Aortic Balloon Occlusion) has been found to facilitate the success of
CPR (cardiopulmonary resuscitation) which has resulted in the cardiac arrest which is
effective in controlling the traumatic hemorrhage. After going through the findings of
this research study, it can be stated that this process has been investigated in various
studying which discussed the effects of ABO on CPR outcomes and the duration of
post-resuscitation of organ protection in a porcine model associated with traumatic
cardiac arrest. The discussion section states that organ protection from damage is a
major aspect of this process. The combination of CCSV and ABO can be stated to
enhance the process of CPR for long term cardiac arrests. This is because of the fact
that the synergistic effects of both the process leads to faster resuscitation and prevents
organ damage. All the CCSV patters has led to a higher partial pressure of oxygen and
was successful in avoiding the pressure drop of arterial blood during the process of
resuscitation. On a concluding note it can be stated that ABO has been successful in the
facilitation of CPR (cardiopulmonary resuscitation) success during a non-traumatic
cardiac arrest. This process has also been found to be successful in controlling traumatic
hemorrhage associated with prolonged occlusion resulting in death and irreversible
organ injury. This paper has first discussed the methodology used to perform the
research followed by the data analysis and expected outcome generation. On a
concluding note, it can be stated that the combination of CCSV and ABO is very much
effective in the process of resuscitation for long term cardiac arrest associated
organisms. Organ damage is also prevented by using this process of treatment for
cardiac arrests. This is the overall effectiveness of this research study. Thus, it can be
stated that all the objectives of the research study have been addressed and the research
can be concluded.
References
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CPR research: a statement for healthcare professionals from a task force of the
American Heart Association, the American College of Emergency Physicians,
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(1996): 2324-2336..
Kill, Clemens, et al. "Chest compression synchronized ventilation versus intermitted
positive pressure ventilation during cardiopulmonary resuscitation in a pig model."
PLoS One 10.5 (2015): e0127759. [Journal].
Kill, Clemens, et al. "Mechanical ventilation during cardiopulmonary resuscitation with
intermittent positive-pressure ventilation, bilevel ventilation, or chest compression
synchronized ventilation in a pig model. [Journal] // " Critical Care Medicine 42.2
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Association guidelines update for cardiopulmonary resuscitation and emergency
cardiovascular care." Circulation 132.18_suppl_2 (2015): S315-S367. [Journal].
Tan, Dingyu, et al. "Advances of ventilation during cardiopulmonary resuscitation."
Chinese Critical Care Medicine 28.7 (2016): 661-665. [Journal].
Xu, Jiefeng, et al. "Miniaturized mechanical chest compressor improves calculated
cerebral perfusion pressure without compromising intracranial pressure during
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Auinger, Daniel, et al. "Invasive blood pressure monitoring during cardiopulmonary
resuscitation–a timeline." Resuscitation 142 (2019): e41-e42.
Daley, James, et al. "The role of resuscitative endovascular balloon occlusion of the
aorta (REBOA) as an adjunct to ACLS in non-traumatic cardiac arrest." The American
journal of emergency medicine 35.5 (2017): 731-736.
Gondek, Stephen, Mary E. Schroeder, and Babak Sarani. "Assessment and resuscitation
in trauma management." Surgical Clinics 97.5 (2017): 985-998.
Kill, Clemens, et al. "Chest compression synchronized ventilation versus intermitted
positive pressure ventilation during cardiopulmonary resuscitation in a pig
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Kill, Clemens, et al. "Influence of mechanical ventilation with Chest Compression
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Kill C, Thonke R, Hahn O, et al."Cerebral oxygenation during resuscitation: influence
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intermitted positive pressure ventilation (IPPV) and of vasopressors on cerebral tissue
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Makhni, Melvin C., et al. "Sudden Cardiac Arrest (SCA)." Orthopedic Emergencies.
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Martínez-Mesa, Jeovany, et al. "Sampling: how to select participants in my research
study?." Anais brasileiros de dermatologia 91.3 (2016): 326-330.
Pietilä, Anna-Maija, et al. "Qualitative Research: Ethical Considerations." The
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Xu, Jiefeng, et al. "The effects of the duration of aortic balloon occlusion on outcomes
of traumatic cardiac arrest in a porcine model." Shock 52.3 (2019): e12-e21.
Dersch W et al. Resuscitation and mechanical ventilation with Chest Compression
Synchronized Ventilation (CCSV) or Intermitted Positive Pressure Ventilation (IPPV).
Influence on gas exchange and return of spontaneous circulation in a pig model.
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modes Chest Compression Synchronized Ventilation (CCSV) or Intermitted Positive
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Experimental operation record sheet
No:P201901- Date: / / 2020
CCSV combined with ABO improves resuscitation outcome and alleviated multiple
organs injury following long-term cardiac arrest resuscitation in a porcine Model
Dosage of special drugs: Midazolam 0.4-0.5mg/kg ; Propofol first dose 2mg/kg 、
maintenance 4mg/kg/h;
肾上腺素 20μg/kg;头孢唑啉 1.0g、im、PR 6h and 18h;
Time Process ( Flow chart)
Midazolam ( ) mg im.
Body weight ( ) kg
ECG monitor( )bpm, Temp ( ) ℃, SPO2 ( ) %
Establishment of ear vein access
propofol ( ) mg iv.
Tracheal intubation and ETCO2 monitor (Propofol supplement mg)
Mechanical ventilation initial parameters: T.V. ( ) ml R.R. ( ) bpm FiO2 ( )
%
Surgical procedures: (1) PiCCO catheter was placed in left femoral artery
before and after CA / CPR and ABO catheter was inserted during CA; (2) 7fr
Swan Ganz catheter was inserted into right femoral vein; (3) 7fr Swan Ganz
catheter was inserted into right femoral artery; (4) PiCCO venous catheter was
placed in the right external jugular vein before and after CA / CPR, and the
defibrillation electrode was placed during CA; (5) carotid blood flow
monitoring probe was inserted into right carotid artery; (6) prepare skin on
forehead and paste brain oxygen probe.
Record BL,Monitoring throughout the experiment: ECG/AP/RP/ETCO2/
Cerebral oxygen
Randomized grouping: IPPV group( ) CCSV group( )
IPPV+ABO group( )CCSV+ABO group( )
Ventricular fibrillation 8min(Disconnect the ventilator. )
CPR ( LUCAS Chest compression + ventilator assisted ventilation)
maintenance 8min
1)CPR period,Continuous monitoring of carotid blood flow / coronary
perfusion pressure /ETCO2/ Cerebral oxygen, etc
2)CPR 4min、7min,采集动脉血,检测血气分析
Defibrillation Once (biphasic wave 150 J) ROSC: yes ( ) no ( )
If not recovered, CPR 2 min( ) If not recovered, CPR 2 min( ) If not recovered,
CPR 2 min( )
If not recovered, CPR 2 min( ) If not recovered, CPR 2 min( )
adrenaline 20µg/kg ( ) Times.; (First time at CPR 2 min,Once every 4
minutes)
PR 0min FiO2 21% Recurrent ventricular arrhythmia: Yes ( times) No ( )
PR 15min、1h、2h、4h,Collect arterial blood for blood gas analysis
PR 1h、2h、4h,conduct PiCCO/ Ultrasound / microcirculation / survival
assessment
PR 1h 、 2h 、 4h 、 24h , Venous blood samples were collected and
centrifuged. Plasma / serum were frozen at - 80 ℃
PR 24h,NDS/CPC Scoring and survival records
PR 24h,Midazolam 0.4mg/kg+ Propofol 3mg/kg+10% potassium chloride
10ml Euthanasia, autopsy, acquisition of tissue specimens,
cryopreservation/formalin fixation
Drug
dosage
Propofol pre-CPR mg,post-CPR mg
Autopsy
CPR record table of experimental data for the period.
Date: / / 2020 Experiment no :P201901-
Experiment grouping:IPPV group( )CCSV group( )IPPV+ABO group( )
CCSV+ABO group( )
DAP
(mmHg)
DRA
(mmHg)
CPP
(mmHg)
ETCO2
(mmHg)
TOI
(%)
CBF
(ml/min)
PC 1
PC 2
PC 3
PC 4
PC 5
PC 6
PC 7
PC 8
PC 10
PC 12
PC 14
PC 16
PC 18
Note: PC, chest compression; DAP, diastolic arterial pressure; DRA, diastolic atrial pressure; CPP, coronary perfusion pressure; ETCO2,, end
tidal carbon dioxide partial pressure; TOI, cerebral oxygen saturation; CBF, carotid blood flow
Hemodynamics/ETCO2/cerebral oxygen/carotid blood flow/PiCCO record sheet
Date: / / 2020 Experiment no:P201901-
Experiment grouping:IPPV group( )CCSV group( )IPPV+ABO group( )
CCSV+ABO group( )
HR
(bpm)
MAP
(mmHg)
MRA
(mmHg)
ETCO2
(mmHg)
TOI
(mmHg)
CBF
(ml/min)
BL
PR 0.5h
1h
2h
3h
4h
CCO
(l/min)
SV
(ml)
GEF
(%)
CFI
(l/min)
EVLW
(ml)
PVPI
BL
PR 1h
2h
4h
Arterial blood gas analysis test reports
Neurological Score Record Form (Left: NDS; Right: CPC)
Date: / /2020 Experiment no:P201901-
Experiment grouping:IPPV group ( )CCSV group( )IPPV+ABO group( )CCSV+ABO
group( )
Evaluation
index
Normal
score
24h
Score description
Consciousne
ss
1 point
Consciousness, gait
and eating are
normal, and
respond to human
approach or
restraint
Normal 0
Fuzziness 30
Lethargic 60
2 point
The above-
mentioned response
has slowed down.
Confused 100
Breathing
3 point
Unable to stand,
walk or eat
Normal 0
Abnormal 50
4 point
Vegetative state or
deep coma
Stop 100
Movement
5 point
No reaction to the
surroundings
Normal 0
Slow 10
Very slow 25
No reaction 50
Muscle tone
Normal 0
2 Stiff limbs 25
4 Stiff limbs 50
Stand up
can 0
Can't 20
Walk
Normal 0
unstable 10
Very
unstable
20
Can't walk 30
Binding
Strong
resistance
0
Resistance 20
Mild
resistance
40
No resistance 50
Total score 400

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Research Proposal CCSV+ABO new.pdf

  • 1. Research Proposal Mechanical Ventilation using CCSV combined with ABO improves resuscitation outcome and alleviated multiple organs injury following long-term cardiac arrest resuscitation in a porcine Model Ph.D. Emergency Medicine Zhejiang University Dr. Zafar Ullah Khan Supervisor : Professor Zhang Mao
  • 2. Table of Contents Introduction....................................................................................................................3 Aim and Objectives....................................................................................................6 Methodology..................................................................................................................6 Establishment of animal model..................................................................................6 Animal randomized grouping and intervention .........................................................6 Parameters setting:.........................................................................................................7 Observation indicators: ..................................................................................................7 Expected outcome..........................................................................................................8 Results........................................................................................................................8 Discussion..................................................................................................................8 Conclusion ...................................................................................................................11 References....................................................................................................................13
  • 3. Introduction Background Cardiac arrest (CA), which has a high incidence rate and a high mortality rate, has become one of the major issues of public health worldwide. The data from the Europe and USA has manifested that the initial rates of resuscitation success in non-traumatic and traumatic CA (Cardiac arrest) victims were 40% and 15.4%, and their survival to hospital discharge were 10.4% and 5.1%, respectively. The clinical prognosis of CA victims is still worse in developing countries. Striving to improve the level of clinical treatment of CA has become a major challenge in the field of resuscitation. Clinically, after the CA incident, the treatment mainly includes cardiopulmonary resuscitation (CPR). CPR stage basic life support and post resuscitation organ protection strategy. In recent years with the continuous improvement and enhancement of pre hospital emergency service system, the continuous progress and popularization of CPR technique, and the ability and willingness of the public to participate in resuscitation and treatment were improved simultaneously, and CA patients achieved self-circulation at CPR stage. The ratio of Return of spontaneous circulation (ROSC) has significantly increased. It has been suggested that after experiencing one CA event, the key factors for improving the outcomes of CA victims are to effectively improve the techniques of basic life support during cardiopulmonary resuscitation (CPR) and also enhance the degree of organ protection during the post-CPR care. The aim of cardiopulmonary resuscitation (CPR) is to give the cardiac arrest patient the best chance of achieving a return of spontaneous circulation and survival. At present, the American Heart Association (AHA) and European Cardiopulmonary Resuscitation Council (ECR) update their guidelines on CPR every five years. CPR, as the main treatment for sudden cardiac arrest, includes circulation, airway, breathing, and defibrillation, each of which is important for overall success. However, there are many controversies about when to establish an advanced airway, which ventilation method to choose and how best to set ventilator parameters. At present, there are no recommendations for the best mechanical ventilation strategy during CPR. The most common settings are: VC mode, tidal volume of 6–7 mL/kg, PEEP of 0–5 cmH2O, rate of 10/minute, and 100% oxygen, while turning off inspiratory triggers or adjusting the pressure trigger level to 20 cmH2O or above, and having a high- pressure alarm set to 50 cmH2O. However, the best ventilation modes are still being explored, including pressure-controlled ventilation (PCV), chest compression synchronous ventilation (CCSV), continuous positive airway pressure/pressure support ventilation (CPAP/PSV), and ultra-low tidal volume ventilation. Our survey found that there are a variety of ventilator parameter settings used in Chinese tertiary hospitals. From what mode to use, to Vt, PEEP or FiO2, only the respiratory frequency setting was consistent. The effect of thoracic pressure on
  • 4. hemodynamics and survival rate in patients with CPR is still controversial, and even if hypoxemia has an impact on the survival rate, experimental results are not consistent. findings showed that ventilator parameter settings for CPR patients are very variable, and the relevant ventilation recommendations in the guidelines are not very specific. There are many factors that need to be considered for proper ventilator settings: patient size and weight, comorbidities, the cause(s) of cardiac arrest and so on. But it is worth mentioning that more than half of surveyed physicians still report mistriggers and high- pressure alarms. Mistriggers often means higher respiratory frequencies are given. High-pressure alarms mean that lower tidal volumes are being delivered. This most likely is due to trigger pressures and high-pressure alarms for ventilators not being effectively adjusted during resuscitation. This aspect of ventilator training is should be a productive area for added emphasis. In this research we will focus on new technique of ventilation during CPR i-e CCSV combine with ABO during CPR to improve outcome and decrease post resuscitation organ damage . Chest Compression Synchronized Ventilation (CCSV) mode of ventilation has originated from WEIMANN Emergency which has been found to be revolutionizing during the process of resuscitation. During this process of chest compression, pulmonary vessels and heart are compressed which don’t allows the volume of gas to escape from the lungs and provides support during chest compression (Kill et al.). In comparison to IPPV and BiLevel, CCSV works best with the preset ventilation values without exceeding the preset ventilation pressure during simulated resuscitation. Both the compression depth and the compression frequency were similar during the application of the different ventilation modes. This demonstrated that none of the examined ventilation patterns had a negative impact on the quality of the chest compressions. In the course of resuscitation, CCSV may be considered as an effective ventilation mode. In some animal studies, compared with traditional positive pressure ventilation, this new ventilation mode improves gas exchange, enhances hemodynamics and increases tissue oxygenation Compared with IPPV, in the pig model of cardiac arrest, all CCSV modes lead to higher PaO2 and prevent the decrease of arterial blood pressure during resuscitation (Kill et al.). Therefore, with CCSV the disadvantages of conventional ventilation during cardiopulmonary resuscitation can be prevented and the gas exchange and hemodynamics can be improved demonstrably. ABO (Aortic Balloon Occlusion) has been found to facilitate the success of CPR which has resulted in the cardiac arrest which is effective in controlling the traumatic hemorrhage (Daley et al.). This process has been investigated in various studying which discussed the effects of ABO on resuscitation outcomes and the duration of post-
  • 5. resuscitation of organ protection in a porcine model associated with TCA (traumatic cardiac arrest). REBOA is used as an adjunct in traumatic or nontraumatic CPR, it might be of importance to carefully determine the aortic occlusion level prior to inflation of the balloon. REBOA in cardiac arrest seems to be a promising therapeutic intervention to be investigated in humans, as a primary intervention to achieve ROSC or as a bridge to more definitive care like percutaneous coronary intervention or/and extracorporeal membrane oxygenation. However, the optimal use of REBOA must be further explored in randomized studies. Studies are necessary to determine the effects of continuous aortic occlusion during CPR on hemodynamics, ROSC, long term survival and neurologic outcome. Furthermore, the optimal duration and adverse effects of intra- arrest REBOA implementation remains unknown. The combination of ABO+CCSV in order to recover the pigs from cardiac arrest was very much effective because of their synergistic effects. Research Design: Research design can be defined as the framework of research methods and techniques that can be chosen by a researcher in order to design a methodology for the research study. The design used in this research study is experimental. Experimental research design has been found to be centrally concerned with the data constructing the research which is associated with high causal and internal validity. This research study will use a randomized control trial in which there will be two groups of population (pig models). These groups will be named as the experimental group and an intervention group. The experimental group will be treated with both ABO and CCSV in order to check the resuscitation of long-term cardiac arrest in the pig models. The intervention group will be treated with either ABO, CCSV or IPPV in order to create a comparison with the experimental group. This research design has been selected for this research study because of the fact that it has been used in various other research studies (Auinger et al.). In a similar research study written by Xu et al. it can be said that there is an enhancement in the success rate of cardiopulmonary resuscitation in cardiac arrest when ABO is used. This paper found that post-resuscitation cardiac, neurological dysfunction and other organ damages were milder for the experimental group than the control group which did not use the intervention (ABO). ABO has been found to be augmented associated with the efficacy of CPR after TCA and improved post-resuscitation cardiac and neurological outcomes were observed. Thus, it can be stated that the combination with CCSV will be beneficial for the enhancement of the resuscitation process and protection of organs from damages. This is the overall research design of this research study since it is based on a similar topic.
  • 6. Aim and Objectives The main aim of this study is Chapter 1. To understand the effect of CCSV +ABO on CPR outcome after long-term CA using experimental Porcine model. Chapter 2. To evaluate the effect of CCSV combined with ABO on multiple organs injury and short-term survival prognosis following long-term cardiac arrest resuscitation in a porcine model. Methodology Establishment of animal model All animals were prepared for general anaesthesia. General anaesthesia was started by Ketamine injected intramuscular at dose of 20mg/kg and completed by venous injection of 2 mg/kg propofol. ETT (endotracheal tube) was introduced into the trachea. Later General anaesthesia was maintained by intravenous infusion of propofol at dosage of 4 mg/kg.h and fentanyl at 2mg/kg.h. Ventricular fibrillation (VF) was induced with a right ventricular paced electrode and AC 7.5 to 15V. VF remained untreated for 8 minutes without any ventilation or chest compression. Lucas cardiopulmonary resuscitation instrument was used for continuous chest compression. With the beginning of chest compression at = 8 min, mechanical ventilation was performed for five periods of eight minutes each. Weinman transport ventilator was used to perform mechanical ventilation. 20 microgram/kilogram of adrenaline was administered for 2 minutes of CPR and this process was repeated every four minutes. Defibrillation was performed with 150 Joules of electrical energy once at 8 minutes CPR. When ROSC will not be restored, the CPR will be restarted immediately every two minutes after defibrillation. This cycle is repeated every five times until the resuscitation is successful or fails. Monitor for 4 hours after successful resuscitation: 1) restart mechanical ventilation; 2) continue anesthesia monitoring; 3) maintain normal body temperature at 38 ℃. 5. Observation in pigsty for 20 h. Animal randomized grouping and intervention Experimental group A total of 32 healthy male white pigs weighing approximately 35 kg were randomly divided into 4 groups (group n=8/): 1) group IPPV (intermittent positive pressure ventilation), 2) group CCSV (Chest Compression Synchronized Ventilation), 3) group IPPV+ABO ( aortic balloon occlusion ) and 4) group CCSV+ABO. 1) IPPV group: IPPV ventilation mode was adopted during CPR, and ABO was not implemented.
  • 7. 2) CCSV group: CCSV ventilation mode was adopted during CPR, and ABO was not implemented. 3) IPPV+ABO group: IPPV ventilation mode was used and ABO were implemented during CPR. 4) CCSV + ABO group: CCSV ventilation mode was used and ABO was implemented during CPR. Parameters setting: 1) IPPV mode before resuscitation: FiO2 21%, Vt 8 ml/kg, RR (determined by ETCO2), I:E=1:2, PEEP 0 mm Hg, inspiratory peak pressure 60 mbar; 2) IPPV mode during resuscitation: FiO2 100%, Vt 7 ml/kg, RR 10 /min, I:E=1:2, PEEP 0 mm Hg, inspiratory peak pressure 60 mbar; 3) CCSV mode during resuscitation: FiO2 100%, inspiratory peak pressure 60 mbar, time 265 ms; 4) ABO implementation during resuscitation: During the resuscitation, ABO was used to block the blood flow completely by balloon inflation in the diaphragmatic region of aortae zone I. 5) IPPV mode after resuscitation: FiO2 21%, Vt 8 ml/kg, RR (same as before resuscitation), I:E=1:2, PEEP 3 mm Hg, inspiratory peak pressure 60 mbar. Observation indicators: Observation indicators during CPR 1. Brain indicators: real-time monitoring of cerebral oxygen saturation and carotid blood flow, and use of ultrasound to evaluate cerebral perfusion and jugular arteriovenous blood flow at 1 minute, 4 minutes, and 7 minutes of CPR; 2. Cardiac indicators: real-time monitoring of coronary perfusion pressure, and evaluation of cardiac perfusion and large vessel blood flow using esophageal ultrasound at 1 minute, 4 minutes, and 7 minutes of CPR; 3. Pulmonary indicators: real-time monitoring of ETCO2, Pulmonary electrical impedance tomography. 4. Large circulation indicators: real-time monitoring of heart rate, MAP, RAP; 5. Microcirculation index: real-time observation of sublingual gland microcirculation; 6. Metabolic indicators: detect arterial blood gas (including pH, PO2, PCO2, BE, lactate, etc.) at 4 and 7 minutes of CPR; 7. Record ROSC rate, resuscitation time, frequency of defibrillation and dosage of adrenaline were recorded. Observation indexes after resuscitation 1. Brain indexes: 1) blood samples were collected to detect NSE at 1 h, 2 h, 4 h and 24 h after resuscitation; 2) neurological function (CPC and NDS) were evaluated at 24 h
  • 8. after resuscitation; 3) brain tissues were obtained to evaluate cell apoptosis (TUNEL, caspase-3) at 24 h after resuscitation; 2. Cardiac index: 1) PiCCO was used to evaluate cardiac function at 1 h, 2 h and 4 h after resuscitation; 2) cTnI was detected at 1 h, 2 h, 4 h and 24 h after resuscitation; 3) myocardial tissue was obtained to evaluate cell apoptosis (TUNEL, caspase-3) at 24 h after resuscitation. 3. Lung indicators: (1) at 1, 3, and 6 hours after resuscitation, PiCCO was used to evaluate ELWI and PVPI; (2) at 1, 3, 6, and 24 hours after resuscitation, pulmonary ultrasound score was used; 3) electrical impedance tomography (EIT); 3. Lung parameters: 1) at 15 min, 1 h, 2 h, 4 h after resuscitation, PiCCO was used to evaluate ELWI and PVPI; (2) at 15 min, 1 h, 2 h, 4 h, 24 h after resuscitation, pulmonary ultrasound score was performed; 3) at 15 min and 1 h after resuscitation, pulmonary electrical impedance imaging indexes ( electrical impedance tomography ); were evaluated; (4) Macrocirculation indicators: real time monitoring HR, MAP, RAP; (5) Microcirculation indicators: real time observation of sublingual gland microcirculation; 6. Metabolic index: arterial blood gas (including pH, PO2, pCO2, be, lactic acid, etc.) was detected at 15 min, 2 h and 4 h after resuscitation; 7. Survival outcome: 4 h and 24 h survival rate; 8. Assessment of aortic injury: at 24 hours after resuscitation, aortic tissue from balloon indwelling site was obtained for HE staining to observe the pathological damage. Expected outcome Results 1. CCSV +ABO improves resuscitation outcome , shortened CPR time, reduced the number of defibrillations, decreased the dosage of epinephrine and significantly increased the ROSC rate. 2. CCSV + ABO significantly prevents organ damage because of the synergistic effect of CCSV and ABO. Discussion Cardiac arrest is a condition associated with the sudden loss of blood flow which results from a failure of heart which cannot pump blood effectively. The symptoms have been found to include the loss of consciousness and abnormal breathing. Sometimes a total absence of breathing is also associated with this disorder (Makhni et al.). This process is also known as cardiopulmonary arrest which leads to the loss of
  • 9. consciousness and partial to permanent death of an individual. The same condition has been observed in pig models. The main causes of cardiac arrests are congenital heart disease, cardiomyopathy, diseases associated with heart valves, acute myocarditis which leads to the inflammation of heart muscle. Cardiac arrest has been observed as a devastating event for many years in spite of improving resuscitation practices associated with the mortality who suffer an OHCA (out of hospital cardiac arrest) (Makhni et al). However, some of them has been found to make a good recovery and return home with good life quality. This is first study on CPR to compared the effects of mechanical ventilation by an automated transport ventilator using a new ventilator mode for resuscitation CCSV and ABO combine. Pigs are selected as experimental animals because their metabolism, cardiovascular function and cardiac anatomy are very similar to those of human beings, which has been considered as the best animal for human CPR research (Idr4). Secondly, because ventricular fibrillation is the most common cause of clinical CA, this study chose ventricular fibrillation to induce CA. Moreover, considering that most of the out of hospital patients can only be cured after more than 8 minutes of CA, a stable and feasible long-term CA model will be more conducive to the preliminary basic research of clinical CPR. The animal model will be established by referring to the pig model method in reference (XuJ2) and combining with the requirements of the latest CPR guidelines in 2015 (Neu2). Reviewing the existing clinical or animal studies on ventilation methods, in addition to the contradiction between different experimental results, the difference between different groups in the same experiment is not particularly significant. In addition to the different research programs, for adult patients with cardiac arrest in CPR, compression and defibrillation are in a higher priority than ventilation. This is because in some cases, even without active ventilation, certain arterial oxygen content can be ensured (Tan5). In the first few minutes of cardiac arrest, certain oxygen content can be maintained in the heart and large blood vessels. When chest compressions are carried out soon after cardiac arrest, the residual oxygen in the alveoli can be reduced in a short time It can maintain oxygenation; after compression relaxation, the negative pressure produced by chest rebound can produce passive ventilation; the common wheezing phenomenon in cardiac arrest can also provide additional ventilation; even if the VT of passive ventilation and wheezing produced by compression is lower than normal, it can maintain the appropriate ventilation / blood flow ratio at a relatively low level compared with the lung hypoperfusion during CPR. In addition, most studies choose short-term cardiac arrest model, the body hypoxia is not very serious, the role of ventilation cannot be reflected; and for some asphyxia cardiac arrest, long-term cardiac arrest model, the role of ventilation is more reflected. Therefore, how to choose the best mechanical ventilation strategy at the same time of CPR is still a problem worthy of further
  • 10. discussion, and how to balance the relationship between compression and ventilation is still the key to solve this problem. This research study deals with long term cardiac arrest pig models in order to study the effect of novel resuscitating process CCSV and Aortic balloon occlusion at a time. During the condition of CPR, coronary perfusion pressure has been found to be very important for high resuscitation outcome. CPP was significantly increased following a high resuscitation rate of success in the 30-60 minutes CCSV group that was compared with the control group (Kil). There are very limited studies on the effect of CCSV on resuscitation outcome during non-traumatic cardiac arrest animal model. The study conducted by kill et al (Kil4) shows that the oxygenation and hemodynamics of CCSV model were better than IPPV and bilevel model.A study by kill et al. shows CCSV provides Improved and better hemodynamics, Mechanical ventilation provides favorable conditions for cardiopulmonary resuscitation with safe airway. kill et al. Studied the effects of volume-controlled ventilation (IPPV), bilayer ventilation (BiPAP) and new CCSV ventilation mode on gas exchange and hemodynamics in pig model and found that CCSV mode had better oxygenation and improved hemodynamics. (Kil4). This research study deals with pig models in order to study the effect of two resuscitating process at a time. Human beings have been found to experience chest pain, nausea and shortness of breath before a sudden cardiac arrest. During the condition of CPR, coronary perfusion pressure has been found to be significantly increased after following a high resuscitation rate of success in the 30-60 minutes. CCSV group that was compared with the control group (Kill et al). According to the observations, after the resuscitation process of cardiac arrest, neurological problems and injuries were found to be higher for the model pigs of the control group. A significant milder and less intestinal and renal injuries were observed for the experimental group. The combination of ABO+CCSV in order to recover the pigs from cardiac arrest was very much effective because of their synergistic effects. These factors were measured after the collection of blood gas samples which are drawn from each of the periods named as MAP (mean arterial pressure) and CVP (central venous blood pressure). These two measurements along with other parameters will be continuously recorded. A similar discussion was made on a research paper discussing the same topic as this research study (Kill, Clemens, et al). There are various advantages of using automatic chest compression detections, uninterrupted chest compressions, can be used in mechanical compression devices associated with chest, easier to integrate inside the standard resuscitation procedures, has improved arterial pressure, improved gaseous exchange and also improves the circulation of blood. According to various observations in CCSV mode, a specific mechanical breath is initiated in synchronization with each of the compressions made in the chest. Thus, no gas volume is allowed to escape from the lungs and the lung pressure has been found to provide support to the chest compression
  • 11. (Pietilä et al.). A device known as frequency tachometer has been found to maintain an optimum compression frequency. There is a great advantage of CCSV which states that the ventilation mode can also be used along with devices associated with mechanical chest compressions. Resuscitative endovascular balloon occlusion of aorta is a very significant topic of research on resuscitation since the last years (Pietilä et al.). Resuscitative endovascular balloon occlusion of the aorta has been found to be increasingly used in resuscitation of trauma victims all over the world. This process has been reported to elevate blood pressure followed by limiting the infusion of fluid when various other procedures are aimed at stopping the bleeding. The resuscitative endovascular balloon has been occlusion of the aorta has been found to increase since the last ten years. Conclusion Thus, after going through the study it can be stated that Chest Compression Synchronized Ventilation (CCSV) mode of ventilation has been revolutionizing during the process of resuscitation. In this pig model of cardiac arrest, compared with the non- synchronous intermittent positive pressure ventilation with volume control, the mechanical ventilation with external chest pressure synchronous ventilation can improve the cooperation of arterial oxygen and better maintain arterial blood pressure.ABO (Aortic Balloon Occlusion) has been found to facilitate the success of CPR (cardiopulmonary resuscitation) which has resulted in the cardiac arrest which is effective in controlling the traumatic hemorrhage. After going through the findings of this research study, it can be stated that this process has been investigated in various studying which discussed the effects of ABO on CPR outcomes and the duration of post-resuscitation of organ protection in a porcine model associated with traumatic cardiac arrest. The discussion section states that organ protection from damage is a major aspect of this process. The combination of CCSV and ABO can be stated to enhance the process of CPR for long term cardiac arrests. This is because of the fact that the synergistic effects of both the process leads to faster resuscitation and prevents organ damage. All the CCSV patters has led to a higher partial pressure of oxygen and was successful in avoiding the pressure drop of arterial blood during the process of resuscitation. On a concluding note it can be stated that ABO has been successful in the facilitation of CPR (cardiopulmonary resuscitation) success during a non-traumatic cardiac arrest. This process has also been found to be successful in controlling traumatic hemorrhage associated with prolonged occlusion resulting in death and irreversible organ injury. This paper has first discussed the methodology used to perform the research followed by the data analysis and expected outcome generation. On a concluding note, it can be stated that the combination of CCSV and ABO is very much effective in the process of resuscitation for long term cardiac arrest associated
  • 12. organisms. Organ damage is also prevented by using this process of treatment for cardiac arrests. This is the overall effectiveness of this research study. Thus, it can be stated that all the objectives of the research study have been addressed and the research can be concluded.
  • 13. References Idris, Ahamed H., et al. "Utstein-style guidelines for uniform reporting of laboratory CPR research: a statement for healthcare professionals from a task force of the American Heart Association, the American College of Emergency Physicians, [Journal] // the European Resuscitation Council, the Heart and Stroke Foundation of Canada, the Institute of Critical Care Medicine, the Safar Center for Resuscitation Research, and the Society for Academic Emergency Medicine." Circulation 94.9 (1996): 2324-2336.. Kill, Clemens, et al. "Chest compression synchronized ventilation versus intermitted positive pressure ventilation during cardiopulmonary resuscitation in a pig model." PLoS One 10.5 (2015): e0127759. [Journal]. Kill, Clemens, et al. "Mechanical ventilation during cardiopulmonary resuscitation with intermittent positive-pressure ventilation, bilevel ventilation, or chest compression synchronized ventilation in a pig model. [Journal] // " Critical Care Medicine 42.2 (2014): e89-e95.. Neumar, Robert W., et al. "Part 1: executive summary: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care." Circulation 132.18_suppl_2 (2015): S315-S367. [Journal]. Tan, Dingyu, et al. "Advances of ventilation during cardiopulmonary resuscitation." Chinese Critical Care Medicine 28.7 (2016): 661-665. [Journal]. Xu, Jiefeng, et al. "Miniaturized mechanical chest compressor improves calculated cerebral perfusion pressure without compromising intracranial pressure during cardiopulmonary resuscitation in a porcine model of cardiac arrest. [Journal] // Resuscitation 85.5 (2014): 683-688.. Auinger, Daniel, et al. "Invasive blood pressure monitoring during cardiopulmonary resuscitation–a timeline." Resuscitation 142 (2019): e41-e42. Daley, James, et al. "The role of resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct to ACLS in non-traumatic cardiac arrest." The American journal of emergency medicine 35.5 (2017): 731-736. Gondek, Stephen, Mary E. Schroeder, and Babak Sarani. "Assessment and resuscitation in trauma management." Surgical Clinics 97.5 (2017): 985-998. Kill, Clemens, et al. "Chest compression synchronized ventilation versus intermitted positive pressure ventilation during cardiopulmonary resuscitation in a pig model." PLoS One 10.5 (2015).
  • 14. Kill, Clemens, et al. "Influence of mechanical ventilation with Chest Compression Synchronized ventilation (CCSV) or Intermitted Positive Pressure Ventilation (IPPV) on haemodynamics in a pig model." Resuscitation 85 (2014): S29-S30. Kill C, Thonke R, Hahn O, et al."Cerebral oxygenation during resuscitation: influence of the ventilation modes chest compression synchronized ventilation (CCSV) or intermitted positive pressure ventilation (IPPV) and of vasopressors on cerebral tissue oxygen saturation. Resuscitation”. 2015;96(11):44 Makhni, Melvin C., et al. "Sudden Cardiac Arrest (SCA)." Orthopedic Emergencies. Springer, Cham, 2017. 511-511. Martínez-Mesa, Jeovany, et al. "Sampling: how to select participants in my research study?." Anais brasileiros de dermatologia 91.3 (2016): 326-330. Pietilä, Anna-Maija, et al. "Qualitative Research: Ethical Considerations." The Application of Content Analysis in Nursing Science Research. Springer, Cham, 2020. 49-69. Swain, Jon. "Ethical Considerations in Research and Education." SAGE Publications, 2016. 74-96. Xu, Jiefeng, et al. "The effects of the duration of aortic balloon occlusion on outcomes of traumatic cardiac arrest in a porcine model." Shock 52.3 (2019): e12-e21. Dersch W et al. Resuscitation and mechanical ventilation with Chest Compression Synchronized Ventilation (CCSV) or Intermitted Positive Pressure Ventilation (IPPV). Influence on gas exchange and return of spontaneous circulation in a pig model. Kill C, et al. Cerebral oxygenation during resuscitation: Influence of the ventilation modes Chest Compression Synchronized Ventilation (CCSV) or Intermitted Positive Pressure Ventilation (IPPV) and of vasopressors on cerebral tissue oxygen saturation.
  • 15. Experimental operation record sheet No:P201901- Date: / / 2020 CCSV combined with ABO improves resuscitation outcome and alleviated multiple organs injury following long-term cardiac arrest resuscitation in a porcine Model Dosage of special drugs: Midazolam 0.4-0.5mg/kg ; Propofol first dose 2mg/kg 、 maintenance 4mg/kg/h; 肾上腺素 20μg/kg;头孢唑啉 1.0g、im、PR 6h and 18h; Time Process ( Flow chart) Midazolam ( ) mg im. Body weight ( ) kg ECG monitor( )bpm, Temp ( ) ℃, SPO2 ( ) % Establishment of ear vein access propofol ( ) mg iv. Tracheal intubation and ETCO2 monitor (Propofol supplement mg) Mechanical ventilation initial parameters: T.V. ( ) ml R.R. ( ) bpm FiO2 ( ) % Surgical procedures: (1) PiCCO catheter was placed in left femoral artery before and after CA / CPR and ABO catheter was inserted during CA; (2) 7fr Swan Ganz catheter was inserted into right femoral vein; (3) 7fr Swan Ganz catheter was inserted into right femoral artery; (4) PiCCO venous catheter was placed in the right external jugular vein before and after CA / CPR, and the defibrillation electrode was placed during CA; (5) carotid blood flow monitoring probe was inserted into right carotid artery; (6) prepare skin on forehead and paste brain oxygen probe. Record BL,Monitoring throughout the experiment: ECG/AP/RP/ETCO2/ Cerebral oxygen Randomized grouping: IPPV group( ) CCSV group( ) IPPV+ABO group( )CCSV+ABO group( ) Ventricular fibrillation 8min(Disconnect the ventilator. ) CPR ( LUCAS Chest compression + ventilator assisted ventilation) maintenance 8min
  • 16. 1)CPR period,Continuous monitoring of carotid blood flow / coronary perfusion pressure /ETCO2/ Cerebral oxygen, etc 2)CPR 4min、7min,采集动脉血,检测血气分析 Defibrillation Once (biphasic wave 150 J) ROSC: yes ( ) no ( ) If not recovered, CPR 2 min( ) If not recovered, CPR 2 min( ) If not recovered, CPR 2 min( ) If not recovered, CPR 2 min( ) If not recovered, CPR 2 min( ) adrenaline 20µg/kg ( ) Times.; (First time at CPR 2 min,Once every 4 minutes) PR 0min FiO2 21% Recurrent ventricular arrhythmia: Yes ( times) No ( ) PR 15min、1h、2h、4h,Collect arterial blood for blood gas analysis PR 1h、2h、4h,conduct PiCCO/ Ultrasound / microcirculation / survival assessment PR 1h 、 2h 、 4h 、 24h , Venous blood samples were collected and centrifuged. Plasma / serum were frozen at - 80 ℃ PR 24h,NDS/CPC Scoring and survival records PR 24h,Midazolam 0.4mg/kg+ Propofol 3mg/kg+10% potassium chloride 10ml Euthanasia, autopsy, acquisition of tissue specimens, cryopreservation/formalin fixation Drug dosage Propofol pre-CPR mg,post-CPR mg Autopsy
  • 17. CPR record table of experimental data for the period. Date: / / 2020 Experiment no :P201901- Experiment grouping:IPPV group( )CCSV group( )IPPV+ABO group( ) CCSV+ABO group( ) DAP (mmHg) DRA (mmHg) CPP (mmHg) ETCO2 (mmHg) TOI (%) CBF (ml/min) PC 1 PC 2 PC 3 PC 4 PC 5 PC 6 PC 7 PC 8 PC 10 PC 12 PC 14 PC 16 PC 18 Note: PC, chest compression; DAP, diastolic arterial pressure; DRA, diastolic atrial pressure; CPP, coronary perfusion pressure; ETCO2,, end tidal carbon dioxide partial pressure; TOI, cerebral oxygen saturation; CBF, carotid blood flow
  • 18. Hemodynamics/ETCO2/cerebral oxygen/carotid blood flow/PiCCO record sheet Date: / / 2020 Experiment no:P201901- Experiment grouping:IPPV group( )CCSV group( )IPPV+ABO group( ) CCSV+ABO group( ) HR (bpm) MAP (mmHg) MRA (mmHg) ETCO2 (mmHg) TOI (mmHg) CBF (ml/min) BL PR 0.5h 1h 2h 3h 4h CCO (l/min) SV (ml) GEF (%) CFI (l/min) EVLW (ml) PVPI BL PR 1h 2h 4h
  • 19. Arterial blood gas analysis test reports
  • 20. Neurological Score Record Form (Left: NDS; Right: CPC) Date: / /2020 Experiment no:P201901- Experiment grouping:IPPV group ( )CCSV group( )IPPV+ABO group( )CCSV+ABO group( ) Evaluation index Normal score 24h Score description Consciousne ss 1 point Consciousness, gait and eating are normal, and respond to human approach or restraint Normal 0 Fuzziness 30 Lethargic 60 2 point The above- mentioned response has slowed down. Confused 100 Breathing 3 point Unable to stand, walk or eat Normal 0 Abnormal 50 4 point Vegetative state or deep coma Stop 100 Movement 5 point No reaction to the surroundings Normal 0 Slow 10 Very slow 25 No reaction 50 Muscle tone Normal 0 2 Stiff limbs 25 4 Stiff limbs 50 Stand up can 0 Can't 20 Walk Normal 0 unstable 10 Very unstable 20
  • 21. Can't walk 30 Binding Strong resistance 0 Resistance 20 Mild resistance 40 No resistance 50 Total score 400