Demonstration report on inclusion of hyperbaric oxygen therapy in treatment of COVID-19 severe cases

Demonstration report on inclusion of
hyperbaric oxygen therapy in treatment of
COVID-19 severe cases

Naval Specialty Medical Center Program Team
Clinical reports and pathologic anatomic findings shown,
progressive hypoxemia is the main cause of deterioration in patients with
COVID-19."The mortality rate of critical patients in WuHan is close to
60%, and we are trying to solve the problem of hypoxia," Zhong Nanshan
said on 27th Feb. HBOT is the strongest non-invasive oxygen therapy. In
the early stage, 5 cases of severe and critical patients with COVID-19 a
were clinically treated, which proved that the long-term excellent clinical
effect of using HBOT in treating hypoxia was also applicable to
COVID-19 patients. The effect of HBOT is better than breathing
atmospheric high flow oxygen and mechanical ventilation techniques. It
is suggested that promote HBOT as an oxygen therapy treatment for
critically ill patients with COVID-19, which is expected to significantly
improve the treatment efficiency, reduce the medical pressure and the risk
of infection, and decrease the mortality rate of critical patients. It has
practical significance for further accelerating the overall victory of this
epidemic, achieving the most effective treatment and realizing infection
prevention control.
I. Evaluation of the effectiveness of HBOT in oxygen
therapy for critical patients with COVID-19.
1) 5 critical patients showed consistent response to HBOT oxygen
therapy
Zhong Yangling, the director of the Department of Hyperbaric
Oxygen in Wuhan Yangtze River Shipping General Hospital, successfully
carried out HBOT treatment in 5 patients with COVID-19 (2 critical and
3 severe), which got significant results. Case reports of the first patient
have been published. 5 cases clinical analysis data shown:
a) Treatment effect of progressive hypoxemia in severe patients
-Rapid relief of hypoxic symptoms. 5 patients had obvious
symptoms of progressive hypoxia before. After the first session of HBOT,
symptoms such as dyspnea and chest pain are reduced. After the second
session HBOT, the symptoms are basically relieved, and the respiratory
rate decreases gradually, but the shortness of breath after the movement
relieved slowly.
-Rapid correction of hypoxemia. Arterial blood gas analysis of 5
patients under the condition of breathing oxygen with oxygen mask
（5~8L/min）before HBOT treatment showed PaO2 is 37, 65, 60, 78, and
68 mmHg, the trend of critical patients’ Blood oxygen saturation of artery
blood of finger(SO2)was reversed immediately. Since the 5th day,SO2
was up to 95% in daily average(1). Compare with the patients’ body data
before they do the HBOT treatment,which be regard as the last day data,
SO2 showed a significant upward trend day by day(2 left). After HBOT
treatment, SO2 is higher than 93%, and every treatment solved the
patient's problem of total hypoxia. Arterial blood gas index recovered
significantly(pic 2 right).
(pic 1)Changes of critical patients’ SO2 before and after HBOT (11/2)
(pic 2) SpO2 daily changes and Arterial blood gas analysis of 5 patients before and after HBOT
b) Comprehensive therapeutic effect of HBOT oxygen therapy
on severe patients
- General condition reversal. In addition to the relief of hypoxic
symptoms in all patients, the general state was significantly reversed.
Gastrointestinal symptoms are reduced and appetite is restored. Headache
disappeared and mental state improved.
- Clinical objective indicators improved. Except the significant
changes in artery blood of finger and Arterial blood gas, differential blood
count, which respond to immune function recovered gradually,
coagulation index of reactive peripheral circulation disorder improved,
Indexes reflecting liver function and myocardial injury improved(3).
- Improved lung pathology. Re-examination of the lung CT after
treatment showed that lung inflammation in all 5 patients was
significantly improved(4).
(pic 3) Changes of coagulation function and sacral hydration in 5 patients before and after HBOT
treatment
(pic 4) CT changes before and after 4-7 HBOT in 5 patients
2) The mechanism of HBOT oxygen therapy
The difference between HBOT oxygen therapy and normal pressure
oxygen therapy is, in general, the use of high pressure oxygen inhalation,
which fully and substantially improves the efficiency of oxygen transport
from the outside to the whole tissue cells. The mechanism of HBOT is to
take advantage of the physical characteristics of gas, to increase the
partial pressure of the oxygen in the environment through a large
amplitude, and to reduce the demand for oxygen exchange and
transportation in the body to achieve the best oxygen therapy effect. The
mechanism of HBOT is shown in pic 5. The advantages compared with
atmospheric pressure oxygen therapy technology are:
Firstly, more effectively than normal pressure oxygen inhalation to
overcome lung tissue inflammation.
The diffusion rate and distance of high pressure oxygen are several
times that of normal pressure oxygen, which overcome the gas exchange
obstacle caused by the thickening of the lung tissue inflammation.And
because of the higher solubility, the amount of oxygen dissolved in the
blood is several times that of atmospheric oxygen, which also further
overcomes the influence of the blood circulation gas ratio.
Secondly, it is more effective to increase oxygen partial pressure than
to increase oxygenation index by mechanical ventilation.
In respiratory and critical care medicine, oxygen efficiency in
clinical respiratory support uses oxygenation index (is the ratio of partial
pressure of oxygen in the artery to partial pressure of oxygen in the
inhaled gas [OI=PaO2/FiO2(air pressure /760)])) as the final evaluation
index. With partial arterial oxygen pressure as the therapeutic target, the
conversion formula[PaO2=OI × FiO2(air pressure /760)]. Mechanical
ventilation technique is to improve PaO2 by increasing OI. The FiO2 of
HBOT can be increased by 1.6~2.8 times. It can be predicted that PaO2
can be increased by 1.6~2.8 times with HBOT patients' OI unchanged,
which is the same as the effect of OI increased by 1.6~2.8 times. The
effects of OI and treatment before treatment in 5 patients have been fully
verified. In one case, HBOT was used to reverse hypoxia on the basis of
no effect of noninvasive mechanical ventilation for 2 days. HBOT
technology for patients with invasive mechanical ventilation is mature
and has been routinely used in clinical HBOT. Therefore suggested that
clinical selection principles are: (1) HBOT treatment is preferred when
patients' oxygenation index is significantly reduced and natural
respiration is clear, and mechanical ventilation is not expected to increase
oxygenation index by 1.5 times; (2) When the improvement of
oxygenation index under mechanical ventilation is less than twice that of
natural respiration, it is suggested to increase the daily HBOT treatment
on the basis of mechanical ventilation.
Thirdly, more effective than ECMO in improving tissue cell oxygen
uptake.
Although ECMO has surpassed the ventilation and gas exchange
functions of the lungs, and can make Hb completely saturated, it is not as
good as HBOT in tissue side oxygen supply. The dissolved oxygen in the
blood has exceeded the amount carried by Hb, and the diffusion distance
has been greatly increased, which can relatively overcome the peripheral
circulation obstacles caused by pre-hypoxic damage or / and infectious
inflammation, and improve the efficiency and absolute amount of tissue
cells to obtain oxygen.
Fourthly, there is no serious interference of mechanical ventilation to
the respiratory tract in natural breathing.
HBOT means that the patient is under high pressure. The common
metaphor of the difference between breathing mode and atmospheric
pressure is that breathing on the plateau is the same as breathing on the
plain, which is natural breathing. Different from mechanical ventilation, it
has a great effect on respiratory tract, need to be paid attention to and
dealt with by doctors and nurses at all times. Otherwise, it is easy to have
various complications such as airway injury.
Fifthly, there is no conflict with the current means of critical treatment,
and the +HBOT mode has a clear role in improving the treatment
effect.
COVID-19, in addition to antibodies and vaccines, there is no
specific drug. All clinical treatment is basically symptomatic treatment
and supportive treatment. HBOT is not the etiological treatment of
COVID-19, it is the symptomatic treatment of hypoxia in patients with
COVID-19, and it is a supplement to the existing oxygen treatment
technology. In addition to HBOT once a day for 95-120 minutes, the
patients also received the existing comprehensive treatment in ICU,
including mechanical ventilation. In addition to HBOT, ICU clinicians
are still responsible for the daily comprehensive treatment of the
above-mentioned severe patients. There is no conflict in treatment
technology. On the contrary, it can provide better support for other
supportive treatments.
(pic 5 The effect of different oxygen therapy on oxygen from the external environment to the
process of tissue and organ)
3) Clear indications of HBOT for the symptomatic treatment of
hypoxia
Firstly, hypoxia is the first indication of HBOT.
HBOT is a routine oxygen therapy for clinical refractory hypoxia.
HBOT has been widely used in the clinic for more than half a century
since it was first used in the supportive treatment of thoracic surgery in
1956. In China, grade A hospitals are generally equipped with oxygen
Chambers, and a large number of HBOT of various diseases are carried
out on a daily basis, especially for carbon monoxide poisoning -- a typical
acute anoxia, which has become a key treatment measure. From the
perspective of diseases, HBOT has a wide range of indications. As a
routine application of oxygen therapy, the indication is essentially a
"hypoxia", that is, generalized and local stubborn hypoxia problem.
Secondly, the diagnosis of anoxia in severe patients with COVID-19 is
clear.
The clinical manifestations of severe patients with hypoxia are
prominent, the indication of hypoxemia is obvious, and the existence of
hypoxia is obvious. In all the previous published clinical scientific
literature on COVID-19, it is clear that the continuous and progressive
development of hypoxemia is an important manifestation of disease
deterioration. In the severe treatment of COVID-19, HBOT is used for
the symptomatic treatment of anoxia correction with clear indications.
The therapeutic effect of 5 patients was very significant, and both
the subjective and objective clinical indexes showed that the deterioration
of hypoxia was interrupted immediately and then the whole body
recovered gradually after the first HBOT. Such a consistent treatment
response, according to the statistical law, cannot be explained by chance.
The above mechanism demonstrated that the efficacy of HBOT in 5
patients was not accidental. The therapeutic effect of HBOT on hypoxia is
a scientific summary of the effects of HBOT in the treatment of
intractable and refractory hypoxia in various diseases over a long period
of time. The relevant scientific papers, literature and works are endless.
The superiority of HBOT in solving severe hypoxia in patients with
COVID-19 is clearly scientific. Unlike the newly developed treatment
stage or the efficacy of medicine is still in the scientific hypothesis stage,
HBOT don't need clinical trial verification and other methods of oxygen
therapy that have been used clinically, such as mechanical ventilation or
ECMO, it can be reasonably used.
In summary, the use of HBOT can provide clear clinical benefits for
the pathophysiological problems encountered in the treatment of hypoxia
in severe critical diseases. HBOT can be used to treat severe hypoxia in
patients with COVID-19, which can more effectively and
comprehensively solve the problem of hypoxemia than normal pressure
oxygen therapy (high flow oxygen inhalation, mechanical ventilation),
make deep tissue hypoxia fully corrected and greatly relieve systemic
hypoxic inflammation, and also has practical clinical significance for the
effects of other treatment methods (such as medicine supportive
treatment).
II. Safety of HBOT for oxygen therapy in severe
patients with COVID-19
HBOT has been standardized and widely used clinically for nearly a
century. Its essential medical safety is not repeated here. The focus is on
disease prevention and control (CDC) risks posed by Class A infectious
diseases. HBOT treatment requires special equipment and procedures,
and patients need to be transferred back and forth from the ward to the
hyperbaric oxygen chamber. The transfer process is in an atmospheric
environment, and there are mature CDC measures without
insurmountable technical problems. Wuhan Changjiang General Hospital
has already formed a practicable method, which can be further improved,
and it will not be repeated here. This article focuses on the treatment
process of HBOT in the oxygen cabin and the risk of CDC in the
hyperbaric oxygen department.
1) . The risk of pathogenic microorganism infection in cabin is not
higher than the ward
Firstly, the risk of performing CDC in the hyperbaric oxygen chamber is
the same as the risk of CDC in the infection ward.
The difference between the micro-environment of the hyperbaric oxygen
chamber and the micro-environment of the infection ward is the radon
pressure.It is same as the difference between the plateau and sea level.
The medical staff is exposed to the oxygen chamber micro-environment
under a high pressure, the surface intensity of pressure is equal, and the
pressure difference cannot be felt. Protective equipment also does not
suffer from “compressive” deformation. The requirements for the
infection control of the hospital in plateau area are not different from
those in the plain area. There are no clear differences in CDC
requirements for different environmental pressures. The process of
medical treatment in the hyperbaric cabin did not significantly increase
the risk of CDC compared with the same operation in the infection ward.
Secondly, the hyperbaric oxygen cabin is a completely new wind
environment.
In the HBOT process, “ventilation” measures are usually adopted.
The pressure valve and the pressure relief valve are opened at the same
time.When the amount of air input is equal to the amount of air output,
the intensity of pressure in the cabin is guaranteed to be constant, and the
air purge inside cabin is continuously updated. The air inlet port and
output port are located on the opposite sides of the cabin. Under
continuous ventilation, the air flow in the cabin is generally unidirectional,
similar to a laminar flow operating room. The pressure of the air in the
pipeline decreases gradually from the source to the exhaust port. There is
no back flow of gas under the pressure gradient. The air sources are
filtered, pressurized, and depressurized by an oil-free air compressor
advanced purification device to ensure clean air sources.
Thirdly, air breathed by doctors and patients is relatively separated
inside the cabin.
The patient used a mask of the Bulding in breathing system (BIBS)
to breathe pure oxygen after entering the cabin. The exhaled gas of the
patient mainly exists in the oxygen exhaust line and flows
unidirectionally outward. Medical staff breathes air in the cabin, basically
does not cross the gas that the patient breathe. This is better than the
infection ward.
Medical staff pressurize independently. During the pressurization
process, the pressure on the body side of the protective equipment is low,
and the air in the cabin may enter the body side of the protective
equipment as the pressure increases. The hyperbaric oxygen chamber is
provided with a transition cabin (small cabin). The medical staff use
independent cabin to pressurize to avoid the possibility that a large
amount of air from the treatment cabin where the patient is regarded as a
contaminated area enters the body side of the protective equipment. The
decompression process is the opposite, so there is no risk of CDC.
Fourthly, Infection ward CDC measures are used in the hyperbaric
oxygen chamber and no additional evaluation is required.
The hyperbaric oxygen chamber is managed as a ward for patients
with new coronavirus. Disinfection process is performed under normal
pressure, and the disinfection technology method and effect are the same.
The pressurization process is with "full fresh air systems", the air that
doctors and patients breathe is relatively independent, and the possible
gas pollution is less than that of infected wards. In addition, the CDC
requirements for infection wards are applicable to infection-control
management after the pressure in the hyperbaric chamber is relatively
constant.
2). Hyperbaric Oxygen Department's measures to control infection
have been initially formed and practical
The Hyperbaric Oxygen Department is an area for the treatment of
infected patients. There are clear rules and regulations for the setting of
the ward isolation area and personnel protection under normal pressure,
which can a reference. It has also formed a set of effective practices,
which will not be repeated here. The focus of controlling infection is to
purify and sterilize the exhaust gas from the BIBS system oxygen outlet
and chamber decompression outlet of the patient's breathing. In this
regard, no products were found at home or abroad for hyperbaric chamber
exhaust gas purification and disinfection. We first adopted strict control
measures in the area of the exhaust port to avoid the possible impact of
the patient's exhaled gas on the outside activities in the effective area. At
the same time, non-standard disinfection measures were temporarily
adopted, and the exhaust gas was filtered by the disinfectant solution to
further prevent the pollution of the exhaust gas to the surrounding
environment and cause the virus to spread. At present, the hyperbaric
chamber supplier has purchased the medical gas purification equipment
certified by the relevant national authorities for modification. After
installation, it can meet the national standards.
To sum up, the hyperbaric oxygen chamber is a closed gas
management system with unidirectional air flow, full fresh air systems,
and separate air pipelines for medical staff and patients to breathe. There
are no insurmountable technical obstacles to the treatment of HBOT for
CDC. Hyperbaric Oxygen Department of Wuhan Changjiang Shipping
General Hospital has established a complete infection control procedures
and measures for HBOT treatment of patients with new coronavirus, and
has passed the evaluation of the infection control department. The HBOT
treatment for patients with severe disease has been carried out more than
20 times in the early stage, and none medical was infected. In general, the
risk of infection in the HBOT chamber is not as high as the ward. Early
intervention of HBOT can reduce the use of mechanical ventilation and
accelerate the cure of critically ill patients, and further reduce the risk of
infection for medical staff.
III. Feasibility Evaluation of HBOT Oxygen Therapy
at Huoshenshan Hospital for COVID-19
Huoshenshan Hospital will be the last line of defense for COVID-19.
The above discussion shows that it is obvious that HBOT can be used for
oxygen therapy in patients with COVID-19 if it can exert its clinical
significance. But Huoshenshan hospitals are not equipped with HBOT
equipment, which is the biggest problem with HBOT. Given that the
treatment of hypoxia is a key and difficult point in the current severe
treatment, it is of practical significance to strive for HBOT oxygen
therapy in Vulcan Hospital. The following preliminary suggestions are
made on the feasibility and progress of Huoshenshan Hospital's existing
treatment + HBOT.
Step1. Portable high-pressure oxygen equipment is used in a small
area, and a basic treatment process adapted to the actual
situation of Huoshenshan Hospital is formed.
In addition to the hyperbaric oxygen chamber, the equipment that
can inhale oxygen at high pressure also has a diving chamber for treating
decompression sickness. The military-equipped electric diving
pressurized chamber and portable High-pressure chamber can also treat
decompression sickness, and can be performed automatically in a good
oxygen environment in a short time(120min) without the help of medical
staff.
A military university in Wuhan is equipped with a mobile diving
chamber (for two people) and a portable hyperbaric oxygen chamber.
Therefore, hyperbaric oxygen therapy can be performed in the open area
of the hospital. This part of the area is controlled according to the
contaminated area and meets the CDC. It is recommended that the
equipment and operator be transferred to Huoshenshan Hospital together
to try HBOT treatment for 5 critically ill patients with similar conditions.
Basic treatment procedures and CDC procedures include:
(1) HBOT treatment: 1.6ATA / 120 minutes, continuous oxygen
inhalation. It is expected to achieve an oxygen therapy effect of 1.6 times
the oxygenation index, which is superior to mechanical ventilation, the
reasonable use of atmospheric oxygen, and the overall therapeutic effect
is significant.
(2) CDC process of HBOT treatment: The CDC process of hyperbaric
oxygen therapy in Wuhan Changjiang Shipping General Hospital has
been proven to be feasible in time, and can be optimized and adjusted
according to the actual layout of Huoshenshan Hospital.
(3) HBOT emergency treatment plan: HBOT uses 1.6ATA, diving
depth is about 6 meters, no decompression is needed. Once the patient's
condition has changed, it can be removed from the compression chamber
within 3 minutes. What you need to do is prepare first aid at atmospheric
pressure next to the oxygen chamber, and then take the patient back to the
ICU ward.
Step2. Concentrate portable hyperbaric oxygen equipment inside
and outside the army to popularize HBOT oxygen therapy as much
as possible
After researching the mobile high-pressure system capable of
treating decompression sickness and combining the number of military
equipment, preliminary estimates are that it can increase 144 times/day
HBOT.
Step3. Hyperbaric Oxygen Chamber Construction at Huoshenshan
Hospital Simultaneously Started
Construction of a new hyperbaric oxygen chamber system started at
Huoshenshan Hospital. After investigation, the supplier of hyperbaric
oxygen equipment of Wuhan Changjiang Shipping General Hospital can
complete the installation and commissioning and put it into use within 15
days. HBOT oxygen therapy for tracheal intubation mechanical
ventilation patients can be further developed and combined with portable
hyperbaric oxygen equipment, the overall effect will be very significant.
Conclusion
In general, HBOT oxygen therapy has clear indications for patients
with COVID-19, with obvious effects and no obvious uncontrollable
safety risks. Control measures and procedures have been developed to
meet the course of treatment for patients with Class A infectious diseases.
The risk of infection by medical staff is not greater than that of infected
wards. HBOT oxygen therapy is widely used, and some hospitals are also
equipped with a hyperbaric oxygen chamber. Therefore, we strongly
recommend including HBOT in the treatment of COVID-19 in order to
provide the treating physician with more effective oxygen therapy.
Huoshenshan Hospital, as the last line of defense for new serious
treatment, is gradually exploring and developing large-scale HBOT
oxygen therapy, which is expected to significantly improve treatment
efficiency, reduce medical and infection pressure and reduce mortality.