Application Registration Study of ILE in Patients With Acute Poisoning
Conditions: Acute Poisoning
Sponsor: Peking Union Medical College Hospital

Registration study on the Application of
intravenous lipid emulsion in patients with
acute poisoning
2021-11-12

Study Protocol
1.Research background and purpose: research status at home and
abroad, preliminary research basis
1.1 Research Background:
Poisoning refers to the occurrence of a series of reactions in
the body tissues after exposure to chemical substances, resulting in
permanent or temporary damage to the structure and function of
human organs, or even serious threats to the patient's life, resulting
in death.The severity of poisoning is determined by the type of
chemical substances, which can be divided into subacute poisoning,
chronic poisoning and acute poisoning. Among them, acute
poisoning has the largest damage and rapid onset, and has a great
impact
on
patients'
health.Therefore,
mastering
the
clinical
characteristics of poisoning events can play a beneficial role in the
further selection of emergency treatment plan.
Fat-soluble drugs is insoluble in water and soluble in fat and
carbon tetrachloride, glycerin, grease and other organic solvents,
drugs, it to each other with the phospholipid bilayer membrane
fusion, easy to absorb, and compared with the water-soluble drugs
are more likely to be through the liver metabolism, metabolic
product by kidney, it has high utilization rate in clinic.However, in
recent years, due to the improper use of fat-soluble drugs, patients

often suffer from fat-soluble benzodiazepines sedative hypnotics,
fat-soluble calcium channel blockers and β -blockers, fat-soluble
tricyclic antidepressants and other intoxication, which poses a
serious
threat
to
the
safety
of
patients.In
addition,
organophosphorus pesticide (fat-soluble) in our country has a high
utilization rate, severe organophosphate poisoning leads to multiple
organs injury, treatment will cause death or disability, clinical
treatment mainly gastric lavage, oxygen and other conventional
treatment, and cooperate with medical drugs and blood dialysis,
blood perfusion treatment, has obtained the certain effect, but the
mortality rate is still high,Therefore, it is of great significance to
explore more safe and effective treatment methods.
Lipid emulsion is the fat component used in total parenteral
nutrition.Vein with fat emulsion (intravenous lipid emulsion, ILE)
used in the treatment of cloth than the original because of local
anesthetics, later also used to treat a variety of other lipotropy drug
poisoning.The treatment of ILE is still in the preliminary stage and
relatively limited.System evaluation to the treatment of acute
poisoning of fat emulsion, found that support the overall quality in
the research on the treatment of low or very low, but in the case
report suggests that fat emulsion of verapamil, beta blockers, some
tricyclic antidepressants, cloth than paid, chlorpromazine, and some

anti-arrhythmic drugs (such as, fluorine carney) poisoning patients
have certain benefits].ILE may help treat hemodynamic instability in
patients who have been poisoned by these drugs.
Possible adverse reactions of standard ILE treatment include
hypertriglyceridemia,
fat
embolism,
infection
and
hypersensitivity.Although these and other potential complications
of ILE treatment have been reported, further studies are needed to
determine the risk of complications from restricted ILE treatment in
acute CCB overdose.
There are several speculations about the mechanism of ILE
efficacy.The first mechanism is that fat emulsions act as a "lipid
pool" that surrounds and disables lipophilic drug molecules.The
second mechanism is that fatty acids in ILE provide a ready-made
energy source for myocardium, thus improving cardiac function .In
addition, ILE may act as a "lipidshuttle," wrapping toxins and
transporting them to the liver and/or kidneys for metabolism.
In view of the fact that the research on the treatment of ILE still
needs to be further improved and related adverse reactions need to
be further discussed, we plan to launch a registered research
program on the application of ILE.
1.2 research objectives :
(1) to study the therapeutic effect of ILE on acute poisoning of

fat-soluble substances.
(2) Further elucidate the related mechanisms of ILE in the treatment
of fat-soluble drug poisoning.
(3) Standardize the relevant process of ILE detoxification treatment.
(4) Further explore the adverse reactions and coping strategies of
ILE treatment.
2.1 Research subjects: According to the indications of ILE treatment
poisoning in clinical toxicology, research subjects were divided into
the following categories :
(1) calcium channel blocker poisoning
(2) β blocker drug poisoning
(3) tricyclic antidepressant poisoning
(4) the organophosphorus fat-soluble pesticide poisoning, such as
bromine phosphorous, chlorpyrifos, and c, fenitrothion diazinon,
methidathion, quetiapine phosphorus, butyl, thiazole phosphorus,
oxygen pyrimidine phosphorus dimethoate, destroy the line p line,
sulfur, phosphorus, and triazophos ethion, sulfoxide, phosphorus,
sulfur, phosphorus, imines phosphorus worm, pyrazole fluorine
sulphur phosphorous, isocarbophos, phorate, methyl parathion,
parathion, dichlorvos, fenitrothion, etc.
(5) local anesthetic poisoning
(6) poisoning of other fat-soluble substances

2.1.1 Sample size At least 500 patients are planned to be included
as observational subjects.
2.1.2 inclusion criteria :
(1) patients diagnosed with acute exposure to fat-soluble drugs and
organophosphorus (fat-soluble) pesticides
(2) patients who failed conventional treatment, especially those
with circulatory failure, such as ventricular arrhythmia, shock, and
cardiac arrest, requiring intravenous fat milk treatment.
(3) non-allergic to lipid emulsion.
(4) signed informed consent.
2.1.3 exclusion criteria:
(1) patients with combined major organ dysfunction;
(2) patients complicated with malignant tumor;
(3) serious mental disorders affect the treatment;
(4) Incomplete clinical data.
2.2 Research design and methods:
When the fat emulsion infusion can cause serious adverse
reactions, in combination with fat emulsion used for oral fat soluble
drug poisoning guidelines [11], in accordance with the association
of American medical toxicology 2016 recommended the latest plan
for detoxification, fat emulsions as fat soluble drug poisoning causes
hemodynamic instability, consider using to treat fat emulsion,

specific plan:①The first dose was given 1.5 mL /kg 20% fat milk for
longer than 2-3min. If there was no reaction, it could be
repeated.②then, the injection was continued at the rate of
0.25ml/(kg.min) and the efficacy was evaluated after 3min. If the
efficacy was obvious, the dose was adjusted to 0.025ml/(kg.min)
and the blood pressure, heart rate and other hemodynamic
parameters were observed at least every 15min.③If there is cyclic
instability again when pushing at the speed of 0.025ml/(kg.min), the
speed can be increased to 0.25ml/(kg.min), and in serious cases, the
load can be pushed again
2.3 Statistical Methods
SPSS19.0 statistical software was used for data processing, and
t test was used for measurement data.P<0.05 was considered
statistically significant.The main efficacy indicators were provided
with sample number, mean, standard difference and other statistics,
and paired T-test (or the signed rank test of paired samples) was
adopted.Descriptive statistics were used to summarize the data of
secondary efficacy indicators, and sample number, mean and
standard
deviation
were
used
for
continuous
variables.The
classification
variables
were
the
number
of
cases
and
percentage.The paired T-test (or the signed rank test of paired

samples)
was
used
to
analyze
continuous
variables.The
McNemar-bowkers test was used to analyze ordered variables.The
efficacy analysis of this study was conducted using the full analysis
set (FAS). Subjects who were unable to provide post-treatment
efficacy data were excluded from the full analysis set, and the last
data carry-over method (LOCF) was used to fill in the missing
efficacy data.Safety analysis set (SS) was selected for safety analysis.
2.4 Announcement of quality control measures and research results
2.4.1 Research quality control Uniformly formulated data collection
forms, and trained sample collectors before collecting original
data.Data analysis will be performed by other study group members,
and all staff involved in the collection, collation and analysis of data
will sign confidentiality agreements.Subject selection in this study
was determined by two investigators familiar with the intervention
and reviewed by the project lead.Clinical data will be collected and
analyzed by two other investigators.The project leader shall
determine the content of objections during the research process.
2.4.2 End point
2.4.2.1 Primary end point
mortality within 24 hours
2.4.2.2 Secondary end point
(1) Time of circulation stabilization, including time of blood

pressure
stabilization
and
time
of
malignant
arrhythmia
disappearance, etc.
(2) dosage of vasoactive drugs
(3) Mortality of patients at 1 week and 28 days
(4) occurrence of serious complications during ILE treatment
2.4.2.3 Criteria for Termination of the study If the study leader finds
that the investigator seriously or persistently fails to comply with
the protocol and other test procedures, which may interfere with
the correct implementation of the study, the study leader has the
right to suspend the study or abandon relevant study data.In case of
termination of the experiment, the study leader shall provide
relevant written reasons.The study termination criteria include but
are not limited to:
(1) Unexpected, significant or unacceptable risks are found for the
subject;
(2) Major errors were found during the execution of the test;
(3) The research drug/trial treatment is ineffective, or the
continuation of the trial is pointless
2.5 Expenses of subjects This clinical trial was an observational
study, aiming to observe the salvage treatment effect of intravenous
fat milk on fat-soluble drugs and pesticides poisoning, and no
corresponding intervention measures were taken in the treatment

process of patients.Fat milk is used as a life-saving measure only
when the above-mentioned patients are still in critical condition
such as circulatory failure after conventional treatment, so no
financial compensation is given.