Analysis of hyperglycemia due to acute organophosphate poisoning

01

Preamble

Acute organophosphate pesticide poisoning (AOPP) is a common toxic disease in China, with rapid onset, rapid change and high
mortality.
In addition to the decrease in cholinesterase activity during AOPP, a variety of laboratory indicators will also change, such as blood gas indicators, coagulation indicators, myocardial markers, other enzymes, etc
.
In addition, moderate to severe AOPP can also have a serious impact
on glucose metabolism.

02

Case history

The child, 3 years old, complained of abdominal pain 3 hours ago, stool once, and dry
stool.
After defecating, the child fell to the ground, poor consciousness, and family members asked about the possibility of pesticide use (specific drug and dose unknown).

The family stimulated the child to vomit once, which was white mucus and pink foam, and the amount was not much
.

After being given an "oropharyngeal ventilation tube" in the outer hospital, he was escorted to our hospital
by 120 at 0:20.
Physical examination: body temperature 36.
1 °C, pulse 67 times / min, breathing 23 times / min, irregular, blood pressure 107/83mmHg, percutaneous oxygen saturation 84%, unconscious, coma-like, pale skin all over the body, cold limbs, cool to the
wrist, ankle.
The bilateral pupils are needle-like, there is no reflection of light, there is a pesticide smell in the mouth, a large amount of bloody discharge can be seen in the mouth and nose, the breathing sounds of both lungs are low, and a large number of sputum sounds can be heard under the resuscitation air sac
.

Laboratory tests showed that cholinesterase persisted less than 0.
2KIU/L, and blood gas, liver function, myocardial markers, and coagulation indicators gradually deteriorated
.
See table
.
Between 5:00 a.
m.
after admission, the bedside blood glucose meter monitored once an hour, and the blood glucose fluctuated between
5.
50 and 6.
80 mmol/L.
At 5:45, the monitoring results of the blood glucose meter exceeded the upper limit, and the laboratory tested glucose 47.
16mmol/L at 6:29, urine glucose 4+, and 33.
80mmol/L
at 9:30.

Table 1 Summary of laboratory test results of children

Description: "/" indicates that it was not detected
.

From admission to 9:20, the child underwent symptomatic and supportive treatment such as gastric lavage, respiratory tract cleaning, tracheal intubation, continuous positive pressure ventilation of artificial air bags, oxygen inhalation, skin cleaning with clean water, saline expansion, sodium bicarbonate correction of acidosis, insulin hypoglycemia, atropine, phosphoderate to relieve organophosphate poisoning, phenolsulfaethylamide to prevent bleeding, maintain internal environment stability and other symptomatic and supportive treatment, repeated respiratory and cardiac arrest, and after multiple cardiopulmonary resuscitation, he was declared dead
at 11:10.

03

Case studies

The child's organophosphate poisoning was clear, and corresponding treatment and rescue measures were taken in time after admission, but the child's life
could not be saved.
The child's blood glucose level soared from 5.
50 to 6.
80 mmol/L to a maximum of 47.
16 mmol/L within a few hours, and the reasons for the increase in blood glucose were analyzed
here.

The cause of elevated blood sugar is nothing more than increased sources and reduced
routes.
The main sources of glucose are intake, glycogenolysis and xenoschase; The main routes are synthetic glycogen, glycolysis, tricarboxylic acid cycle, gluconeogenesis and direct excretion
through urine.

1.
Stress can affect the source and route of glucose, resulting in changes in blood glucose levels [1].

As a strong stressor, organophosphate pesticides can lead to increased glucagon secretion, enhanced glycogen decomposition and increased xenogenesis; Stress states also inhibit insulin secretion and enhance insulin resistance [2].

(1) AOPP patients have enhanced glycogen decomposition and increased blood sugar sources: after organophosphate poisoning, the nervous system will be in a state of stress and excitement, and after the islet α cells are stimulated by β cells, the poisoned person will secrete more glucagon, which can lead to increased glycogen decomposition [3].

(2) AOPP patients have increased xenosa, blood sugar sources increase: AOPP patients adrenal medulla will accumulate more acetylcholine, acetylcholine can release a large amount of norepinephrine, glucocorticoid secretion increases, protein decomposition after a large amount of decomposition, can strengthen the production of xenogenic sugar [3], will also increase blood sugar
.

(3) AOPP patients have inhibition of insulin secretion, decreased liver glycogen synthesis, and decreased blood glucose pathways: glucagon increases the release of catechol in body tissues, and insulin secretion is inhibited, which can lead to a decrease in liver glycogen synthesis [4].

(4) AOPP patients can develop insulin resistance, inhibit glycogen synthesis, and reduce blood sugar pathways: in critical disease states, insulin receptor function may be abnormal, receptor signal transduction, glucose transport, intracellular metabolism disorders and cytokines may be produced excessively, thereby causing insulin resistance [5], and can also further inhibit glycogen synthesis
.

(5) AOPP can cause multi-organ damage, thereby affecting
the source and route of glucose.
It is believed that AOPP causes multi-organ damage through both cholinergic and non-cholinergic mechanisms, and the role of non-cholinergic mechanisms in the process of organ injury is more obvious
.
Systemic inflammatory response syndrome (SIRS) has been shown to be involved in the pathogenesis of AOPP-induced multiple organ dysfunction syndromes (MODS) [6].

For example, when AOPP causes liver damage, it can lead to a decrease in glucose to liver glycogen; When AOPP causes pancreatic injury, it can lead to inadequate insulin secretion [7].

2.
Lack of oxygen leads to glucose utilization disorders, and glucose accumulates in the body [2].

Possible mechanisms are:

(1) Patients with AOPP have bronchospasm and increased mucus secretion, resulting in insufficient ventilation and ventilation, and hypoxia
in the body.

(2) Severe AOPP can cause acute blood circulation disorders in solid organs such as heart, liver, kidney, skeletal muscle, etc.
, and the ability to use glucose is reduced
.
At AOPP, organophosphorus interferes with cellular metabolic processes, especially glucose and mitochondrial metabolism [8].

AOPP produces too much oxygen free radicals, which can cause chromosome and DNA damage, decreased cell proliferation, increased apoptosis [9], and further aggravated the body's glucose utilization disorders
.

3.
AOPP and blood sugar level: According to the foregoing, in moderate to severe AOPP, there is a vicious circle of blood glucose level regulation feedback: hypoxia leads to glucose utilization disorders, at which time glucose will accumulate in the body, but due to glucose utilization disorders, the body will mobilize more glucose into the blood through a variety of ways, resulting in a sharp increase
in blood sugar levels.

At present, it is believed that in patients with AOPP, blood glucose changes can reflect the strength of stress response and stress process, which can be used as an important reference index for metabolic support of patients [6].

Hyperglycemia can also be used as an early warning indicator of MODS in patients with AOPP [10].

The blood glucose level of patients with AOPP is related to the degree of toxicity, and the more severe the degree of poisoning, the more pronounced the increase in blood glucose [11].

Clinical cases and animal experiments have shown that in patients with AOPP, hyperglycemia is mainly seen in patients with moderate to severe poisoning; Higher blood glucose levels are associated with higher mortality [2,12].

From the summary table of laboratory test results of the child, it can be seen that when the child was admitted to the hospital, PO2 decreased significantly, and there was already hypoxia, but due to the short time, the blood glucose level has not increased
significantly.
With the progression of the disease and the intervention of therapeutic measures, the child's blood gas indicators have improved, but this can only indicate that the ventilation function has improved, and the ventilation function is still decreasing
.

The decrease in PH and the continuous increase in Lac indicate that the child's acidosis is worsening, indicating the ventilation dysfunction of tissue cells, worsening hypoxia, and decreased
glucose utilization.
Persistent elevations in ALT, AST, CK, CK-MB, LDH, and Tn-I indicate aggravated damage to liver, myocardium, and skeletal muscle, respectively, and decreased
glucose utilization.
On the one hand, the continuous decline of protein also indicates the aggravation of liver damage, on the other hand, it also indicates the aggravation of tissue decomposition, which will lead to a decrease in glycogen synthesis and an increase in
xenogenesis.

Deterioration of coagulation indicators indicates the onset of SIRS and MODS, which can further reduce glucose utilization
.
At the same time, due to the stimulation of organophosphorus, the body mobilizes more glucose into the bloodstream, causing blood sugar levels to soar
.
Excessive blood sugar levels exceed the renal glucose threshold, resulting in a significant increase
in urine glucose.

04

Summary

In clinical practice, close attention should be paid to AOPP combined with hyperglycemia, and measures should be actively taken
.
Studies have shown [13-15] that both endogenous and exogenous blood glucose elevations are detrimental to AOPP treatment
.
Hyperglycemia during AOPP can inhibit the chemotaxis, adsorption, and phagocytosis of leukocytes, making patients prone to co-infection or infection difficult to control
.
Hyperglycemia can form a hyperosmolar state, aggravate dehydration and electrolyte imbalance, making treatment more complicated and difficult
.

Hyperglycemia can also cause recurrent
toxinine-like symptoms.
Strict control of blood sugar is conducive to reducing the release of inflammatory factors in the body, thereby reducing tissue damage
.
In clinical treatment of AOPP, hypertonic glucose solution should be used with caution, and if it must be used, insulin
should be added in time.
In conclusion, the monitoring of blood glucose concentration in patients with AOPP can provide useful value
for the judgment of the disease and its outcome.

References

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