Methods for stimulating natural detoxification

Detoxification, carried out as an emergency medical intervention, aims to accelerate the elimination of toxicants from the body, as well as reduce their toxicity during the period of being in the biomeding environment and includes three main groups of methods aimed at stimulating the natural processes of cleansing the body or replacing them (prosthetics) by using methods of artificial detoxification and for the neutralization of toxicants with the help of antidotes. The general scheme of detoxification therapy is presented below.

Methods of stimulation of natural processes of organism purification

Stimulation of excretion

• Cleaning of the digestive tract
  • Emetics (apomorphine, ipecacuana),
  • gastric lavage (simple, probe), gastric lavage (GL),
  • washing of the intestine - intestinal lavage, enema,
  • laxatives (saline, oil, vegetable),
  • pharmacological stimulation of intestinal peristalsis (serotonin)
• Forced diuresis
  • water-electrolyte load (oral, parenteral),
  • osmotic diuresis (mannitol),
  • saluretic diuresis (furosemide),
• Therapeutic hyperventilation of the lungs

Stimulation of biotransformation

• Pharmacological regulation of the enzymatic function of hepatocytes
  • Enzymatic induction (barbiturates, ethanol, reamberin),
  • enzymatic inhibition (chloramphenicol, cimetidine)
• Oxidation enhancement (sodium hypochlorite)
• Therapeutic hypothermia
• HBO

Substitution immunotherapy (immunoglobulins)

• Antidote (pharmacological) detoxification
• Chemical antidotes (toxicotropic)
  • contact action,
  • parenteral action
• Biochemical antidotes (toxic-kinetic)
• Pharmacological antagonists
• Antitoxic immunotherapy (serum)
• Methods of artificial physico-chemical detoxification
• Aferatic
  • plasma-substituting drugs (albumin),
  • hemapheresis (blood substitution),
  • plasmapheresis
• Dialysis and filtration
• Extracorporeal methods
  • DG,
  • GF,
  • OGDF,
  • plasma filtration
• Intracorporal methods
  • PD,
  • intestinal dialysis
• Sorption
• Extracorporeal methods
  • hemo-, plasmosorption,
  • albumin dialysis - sorption according to the method of MARS,
  • application sorption
• Intracorporal methods
  • enterosorption

Therapeutic hyperventilation

Methods of enhancing the natural processes of body detoxication include therapeutic hyperventilation, which can be provided by inhalation of a carbogen or by the use of mechanical ventilation, which allows to increase the minute volume of respiration by a factor of 1.5-2. This method is considered particularly effective in acute poisoning by toxic substances, which are largely removed from the body by the lungs. High efficiency of this method of detoxification for acute poisoning with carbon disulphide (up to 70% of it is secreted by light), chlorinated hydrocarbons, carbon monoxide. However, prolonged hyperventilation leads to the development of violations of the gas composition of the blood (hypocapnia) and CBS (respiratory alkalosis). Therefore, under the control of these parameters, intermittent hyperventilation (for 15-20 min) is performed repeatedly 1-2 hours during the entire toxicogenic phase of poisoning.

Regulation of enzymatic activity

Biotransformation of toxic substances is one of the most important ways of natural detoxification of the body. It is possible to increase the activity of induction of enzymes, mainly in liver microsomes, responsible for the metabolism of toxic compounds, or a decrease in the activity of these metabolites, i.e., inhibition, leading to a slowing of metabolism. In clinical practice, induction drugs or enzyme inhibitors that affect the biotransformation of xenobiotics are used to reduce their toxic effects. Inductors can be used for poisoning with substances, the nearest metabolites of which are significantly less toxic than the native substance.

Inhibitors can be used for poisoning by such compounds, biotransformation of which proceeds according to the type of "lethal synthesis", the formation of more toxic metabolites.

Currently, more than two hundred substances are known that can affect the activity of microsomal enzymes (cytochrome P450).

The most studied inducers are barbiturates, in particular phenobarbital or benzobarbital and a specially formulated flumecinol® preparation. Under the influence of these drugs in the mitochondria of the liver, the level and activity of cytochrome P450 is increased, which is due to stimulation of the processes of their synthesis. Therefore, the therapeutic effect manifests itself not immediately, but after 1.5-2 days, which significantly limits the possibility of their use only those types of acute poisoning, the toxicogenic phase of which develops slowly and proceeds more longly than the above dates. Clinical use of inducers of enzymatic activity is indicated in case of poisoning (overdose) with steroid hormones, coumarinic anticoagulants, steroidal contraceptive agents, pyrazolone group analgesics, sulfonamides, antitumor drugs (cytostatics), vitamin B, and some insecticides (especially subacute poisoning) from group carbamic acid (dioxycarb, pyrimor, sevin, furadan) and organophosphorus compounds (actellic, valexone, chlorophos).

The doses of enzyme activity used in the clinic for inductors are for flumecinol® - 50-100 mg per 1 kg of body weight 4 times a day, for reamberin - 5% solution of 400 ml intravenously 2-3 days. In recent years, the most widely used as inducers of enzymatic activity are methods of chemohemotherapy with the help of sodium hypochlorite infusions, for this purpose, HBO can be used.

As inhibitors of enzymatic activity, many drugs have been proposed, in particular nialamide (monoamine oxidase inhibitor), chloramphenicol, disulfiram, ethanol, etc. However, their clinical effectiveness in poisoning with substances that undergo lethal synthesis in the body is limited, as the inhibitory effect develops on the 3rd-4th day, when the toxicogenic phase of most poisonings is already at an end. When poisoning with methanol, ethyl alcohol is used. There are recommendations for the use of large doses of chloramphenicol (2-10 g / day inwards) when poisoned with dichloroethane and pale toadstool.

Oxidation enhancement

Infusions of sodium hypochlorite (HCN) can significantly accelerate the biotransformation of toxic substances due to the release of active oxygen and chlorine, which intensively oxidize hydrophobic toxic substances and affect the lipid structures of bacterial cell membranes, violating their permeability. In addition, hypochlorite ions modify the activity of oxidative enzymes, thereby simulating the detoxification function of the liver, in particular cytochrome P450. In acute poisoning, the introduction of HCN is also accompanied by a moderate disaggregation of erythrocytes and platelets and an improvement in the oxygenation characteristics of the blood (increased oxygen partial pressure, oxygen saturation, and an increase in the capillary-venous difference in oxygen).

The severity of endotoxicosis decreases due to a rapid decrease in blood levels of "medium molecules".

In the course of therapy with solutions of HCN, it should be taken into account that a solution with a concentration of 300 mg / l has low clinical efficacy, and solutions with a concentration of 1200 mg / l are applied only externally. The optimum concentration of HCN is thus a concentration of 600 mg / l.

The treatment of acute poisoning with sodium hypochlorite

Equipment	The device for electrochemical detoxication of the organism EDO-4
System of highways	One-time special or PC-11-03 (KR-11-01) PK-11-01 (KR-11-05)
Vascular access	Central or peripheral vein catheterization
Preliminary preparation
Hemodilution	Not required
Premedication	Medication and infusion correction of hypoglycemia, hypokalemia and acidosis In addition, before the session - chloropyramine (1-2 ml of 1% solution), prednisolone (30-60 mg) intramuscularly, intravenously
Heparinization	Not required
Method of infusion of HCN	Intravenously drip
The rate of HCN infusion	With isolated application - 7-10 ml / min When used in the extracorporeal circuit - 13 ml / min
The volume of HCN infusion	400 ml
Recommended Modes	When used simultaneously with hemosorption, HCN infusion during the first 30 minutes at the column inlet. For the treatment of methemoglobinemia and alcohol intoxication, a single infusion. With alcoholic delirium, 3-4 daily infusions, in cases of its severe course, up to two infusions of HCN per day. Recommended concentration HCN - 600 mg / l (0.06%)
Indications for use	Clinical poisoning with medicinal preparations, alcoholic delirium, alcohol intoxication, methaemoglobin-forming poisoning Laboratory laboratory signs of endotoxicosis, long exposure of toxic substances in the body
Contraindications	Acute cardiovascular insufficiency (collapse), gastrointestinal bleeding, poisoning with organophosphorus compounds in the toxicogenic stage, hypoglycemia hypokalemia, acidosis, severe blood hypocoagulation
Complications	Neurovegetative (chills, hyperthermia, fluctuations of blood pressure), aseptic peripheral phlebitis

Therapeutic hypothermia

Artificial cooling of the body in order to reduce the intensity of metabolic processes and increase resistance to hypoxia is widely used as a method of symptomatic therapy of acute poisoning in toxic brain edema caused by poisoning with narcotic poisons. From the point of view of the possibility of detoxifying the body, artificial hypothermia has been poorly studied, although there are certain prospects for using its antihypoxic properties in severe exotoxic shock, and also in order to slow the lethal synthesis of methyl alcohol, ethylene glycol, chlorinated hydrocarbons.

Hyperbaric oxygenation

The HBO method has been widely used for the treatment of acute exogenous poisoning.

In determining the indications for HBO, the poisoning stage is of paramount importance. In the toxicogenic stage, when the toxic substance circulates in the blood, HBO can serve as a method to enhance the natural processes of detoxification, but only in cases where the biotransformation of poisons occurs by the type of oxidation with the direct participation of oxygen without the formation of more toxic metabolites (carbon monoxide (II), methaemoglobin-forming substance). On the contrary, HBO is contraindicated in the toxicogenic stage of poisoning with poisons, the biotransformation of which proceeds according to the type of oxidation with lethal synthesis, which leads to the formation of more toxic metabolites (carbofos, ethylene glycol, etc.).

This is a general rule based on the theory of biotransformation of toxic substances in the body.

Before the start of the session, it is recommended to do a chest x-ray, to determine the parameters of the CBS, to record the initial ECG, which is repeated after the session. Taking into account the usually difficult condition of patients with poisoning, compression and decompression in the pressure chamber is carried out slowly (for 15-20 minutes) with a change in pressure, at a rate of 0.1 atm / min. The duration of the patient's stay under medical pressure (1,0-2,5 ati) is 40-50 minutes.

The clinical efficacy of HBO as a method of detoxification is most clearly manifested in its early application to stimulate the process of biotransformation of carboxyhemoglobin in carbon monoxide poisoning, meth- and sulfgemoglobin - when poisoned with nitrites, nitrates and their derivatives. At the same time there is an increase in oxygen saturation of blood plasma and stimulation of its tissue metabolism, which has the character of pathogenetic therapy.

In the development of toxic (posthypoxic encephalopathy in the somatogenic phase of carbon monoxide poisoning, drugs, etc.), the use of gentle HBO regimens (0.3-0.5 ati) with lengthening of course treatment (up to 30 sessions) and duration of the session up to 40 min is recommended.

The relative contraindication to the use of HBO in these poisonings is the extreme severity of the patients' condition, associated with the development of a decompensated form of exotoxic shock requiring intensive therapy to correct the basic parameters of hemodynamics.