Methods of stimulating natural detoxification

Detoxification, carried out as an emergency medical measure, aims to accelerate the removal of toxicants from the body, as well as reduce their toxicity during their stay in biological environments and includes three main groups of methods aimed at stimulating the natural processes of cleansing the body or replacing them (prosthetics) by using artificial detoxification methods and neutralizing toxicants with antidotes. The general scheme of detoxification therapy is presented below.

Methods of stimulating the body's natural cleansing processes

Stimulation of excretion

• Gastrointestinal tract cleansing
  • emetics (apomorphine, ipecac),
  • gastric lavage (simple, tube), gastric lavage (GL),
  • intestinal lavage - intestinal lavage, enema,
  • laxatives (salt, oil, herbal),
  • 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),
  • enzyme inhibition (chloramphenicol, cimetidine)
• Enhanced oxidation (sodium hypochlorite)
• Therapeutic hypothermia
• HBO

Replacement immunotherapy (immunoglobulins)

• Antidote (pharmacological) detoxification
• Chemical antidotes (toxicotropic)
  • contact action,
  • parenteral action
• Biochemical antidotes (toxicokinetic)
• Pharmacological antagonists
• Antitoxic immunotherapy (serums)
• Methods of artificial physical and chemical detoxification
• Apheretic
  • plasma substitutes (albumin),
  • hemapheresis (blood replacement),
  • plasmapheresis
• Dialysis and filtration
• Extracorporeal methods
  • GD,
  • GF,
  • OGDF,
  • plasmafiltration
• Intracorporeal methods
  • PD,
  • intestinal dialysis
• Sorption
• Extracorporeal methods
  • hemo-, plasmasorption,
  • albumin dialysis - sorption according to the MARS method,
  • application sorption
• Intracorporeal methods
  • enterosorption

Therapeutic hyperventilation

Methods of enhancing the body's natural detoxification processes include therapeutic hyperventilation, which can be achieved by inhaling carbogen or using artificial ventilation, which allows increasing the minute volume of respiration by 1.5-2 times. This method is considered especially effective in acute poisoning with toxic substances, which are largely removed from the body by the lungs. This detoxification method is highly effective in acute poisoning with carbon disulfide (up to 70% of it is excreted by the lungs), chlorinated hydrocarbons, and carbon monoxide. However, prolonged hyperventilation leads to the development of disorders of the gas composition of the blood (hypocapnia) and acid-base balance (respiratory alkalosis). Therefore, under the control of the above parameters, intermittent hyperventilation is carried out (for 15-20 minutes) repeatedly every 1-2 hours throughout the 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. In this case, it is possible to increase the activity of enzyme induction, mainly in liver microsomes responsible for the metabolism of toxic compounds, or to decrease the activity of these metabolites, i.e. inhibition, which entails a slowdown in metabolism. In clinical practice, enzyme inducers or inhibitors are used that affect the biotransformation of xenobiotics in order to reduce their toxic effect. Inductors can be used in cases of poisoning with substances whose closest metabolites are significantly less toxic than the native substance.

Inhibitors can be used in cases of poisoning by compounds whose biotransformation occurs according to the “lethal synthesis” type, with the formation of more toxic metabolites.

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

The most studied inductors are barbiturates, in particular phenobarbital or benzobarbital and the specially created drug flumecinol®. Under the influence of these drugs, the level and activity of cytochrome P450 in the liver mitochondria increases, which is due to the stimulation of their synthesis processes. Therefore, the therapeutic effect does not appear immediately, but after 1.5-2 days, which significantly limits the possibilities of their use to only those types of acute poisoning, the toxicogenic phase of which develops slowly and lasts longer than the above periods. Clinical use of enzyme activity inducers is indicated in cases of poisoning (overdose) with steroid hormones, coumarin anticoagulants, steroid-structured contraceptives, pyrazolone analgesics, sulfonamides, antitumor drugs (cytostatics), vitamin B, as well as some insecticides (especially in subacute poisoning) from the carbamic acid group (dioxicarb, pyrimor, sevin, furadan) and organophosphorus compounds (actellic, valexon, chlorophos).

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

Many drugs have been proposed as inhibitors of enzymatic activity, in particular nialamide (a monoamine oxidase inhibitor), chloramphenicol, disulfiram, ethanol, etc. However, their clinical effectiveness in poisoning with substances that undergo lethal synthesis in the body is limited, since the inhibitory effect develops on the 3rd-4th day, when the toxicogenic phase of most poisonings is already ending. In case of methanol poisoning, ethyl alcohol is used. There are recommendations for the use of high doses of chloramphenicol (2-10 g/day orally) in case of poisoning with dichloroethane and death cap.

Increased oxidation

Sodium hypochlorite (SHC) infusions significantly accelerate the biotransformation of toxic substances by releasing active oxygen and chlorine, which intensively oxidize hydrophobic toxic substances and affect the lipid structures of bacterial cell membranes, disrupting their permeability. In addition, hypochlorite ions modify the activity of oxidative enzymes, similarly simulating the detoxification function of the liver, in particular cytochrome P450. In acute poisoning, the introduction of SHC is also accompanied by moderate disaggregation of erythrocytes and platelets and improvement of blood oxygenation characteristics (increase in partial oxygen pressure, blood oxygen saturation, increase in capillary-venous oxygen difference).

The severity of endotoxicosis is reduced due to a rapid decrease in the level of “medium molecules” in the blood.

In the process of therapy with GCN solutions, 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 used only externally. The optimal concentration of GCN is thus a concentration equal to 600 mg/l.

Methods of therapy of acute poisoning with sodium hypochlorite

Equipment	Electrochemical detoxification device EDO-4
Highway system	Disposable special or PC-11-03 (KR-11-01) PC-11-01 (KR-11-05)
Vascular access	Catheterization of central or peripheral veins
Preliminary preparation
Hemodilution	Not required
Premedication	Drug 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 GHN	Intravenous drip
Rate of infusion of GHN	When used in isolation - 7-10 ml/min When used in an extracorporeal circuit - 13 ml/min
Volume of infusion of GHN	400 ml
Recommended modes	When used simultaneously with hemosorption - infusion of HCN during the first 30 minutes at the entrance to the column For the treatment of methemoglobinemia and alcohol intoxication - a single infusion For alcoholic delirium - 3-4 daily infusions, in cases of its severe course - up to two HCN infusions per day The recommended concentration of HCN is 600 mg/l (0.06%)
Indications for use	Clinical drug poisoning, alcohol delirium, alcohol intoxication, poisoning with methemoglobin formers Laboratory laboratory signs of endotoxicosis, long-term exposure to toxic substances in the body
Contraindications	Acute cardiovascular failure (collapse), gastrointestinal bleeding, poisoning with organophosphorus compounds in the toxicogenic stage, hypoglycemia , hypokalemia, acidosis, severe blood hypocoagulation
Complications	Neurovegetative (chills, hyperthermia, blood pressure fluctuations), aseptic peripheral phlebitis

Therapeutic hypothermia

Artificial cooling of the body to reduce the intensity of metabolic processes and increase resistance to hypoxia is more widely used as a method of symptomatic therapy of acute poisoning with toxic cerebral edema caused by poisoning with narcotic poisons. In terms of the possibilities of detoxifying the body, artificial hypothermia has been little studied, although there are certain prospects for using its antihypoxic properties in severe exotoxic shock, as well as to slow down lethal synthesis in poisoning with methyl alcohol, ethylene glycol, chlorinated hydrocarbons.

Hyperbaric oxygenation

The HBO method has found wide application in the treatment of acute exogenous poisoning.

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

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

Before the session, it is recommended to take a chest X-ray, determine the acid-base balance indicators, record the initial ECG, which is repeated after the session. Given the usually severe condition of patients with poisoning, compression and decompression in the pressure chamber are 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 therapeutic pressure (1.0-2.5 atm) is 40-50 minutes.

The clinical effectiveness of HBO as a method of detoxification is most clearly demonstrated in its early use to stimulate the process of biotransformation of carboxyhemoglobin in case of carbon monoxide poisoning, met- and sulfhemoglobin - in case of poisoning with nitrites, nitrates and their derivatives. At the same time, there is an increase in the oxygen saturation of the blood plasma and stimulation of its tissue metabolism, which is of the nature of pathogenetic therapy.

In the development of toxic (post-hypoxic encephalopathy in the somatogenic phase of poisoning with carbon monoxide, drugs, etc.), it is recommended to use gentle HBO regimens (0.3-0.5 atm) with an extension of the course of treatment (up to 30 sessions) and the duration of the session up to 40 minutes.

A relative contraindication to the use of HBO in these cases of poisoning is the extreme severity of the patient's condition, associated with the development of a decompensated form of exotoxic shock, requiring intensive therapy to correct the main hemodynamic parameters.