Successful management of critically ill patients or patients in severe clinical condition depends primarily on the potential recovery response of patient functional systems to the therapeutical procedures. This statement in its major part is attributed to human body systems, responsible for oxygen delivery, oxygen distribution in tissues, and metabolic capacity of cellular elements for adequate oxygen consumption. The quality of medical care for seriously ill patients can be improved by using the whole range of treatment modes aimed for correction of metabolic disorders in tissues, that are induced by hypoxia, activation of free radical oxidation, and progression of endogenous intoxication in the patients.
- COMPOSITION AND PROPERTIES
Reamberin, 1.5% solution for infusion is a balanced polyion solution, which is isotonic, isoionic, and isohydric with respect to plasma. It is used as a detoxifying agent with anti-hypoxic property
- Reamberin, 1.5% solution for infusion contains:
Sodium chloride - 2.400 g Potassium chloride - 0.120 g Magnesium chloride - 0.048 g N-(1-deoxy-d-glucitol-1-yl)-N-methylammonium sodium succinate (Reamberin) - 6.000 g Water for injection - 400 ml
- Major characteristics:
Effect of prompt disintoxication;
Normalization of acid-base balance;
- Addititious activities:
Anti-hypoxic activity Nephroprotective action Anti-oxidative activity Insulinotropic action Normalization of blood flow properties Antitoxic action Antitoxic action Radioprotective activity Hematologic action Anticancer activity Antiuralytic action Immunocorrective activity Cardioprotective action Anti-stress activity Improved microcirculation in organs and tissues Adaptogenic activity Hepatotropic action Stabilization of metabolic processes
The major advantage of Reamberin is the opportunity to perform a high effective metabolic abort of intoxication syndrome.
- Reamberin, 1.5% solution for infusion contains:
- MECHANISM OF ACTION
Preparations containing succinic acid (succinates) In tissue and organ hypoxia during simultaneous decrease in activity of Krebs cycle enzymes exogenous succinic acid is utilized via alternative route of succinate dehydrogenase system during which the preferential utilization of succinic acid as substrate for oxidation in mitochondrial respiratory chain takes place (Fig. 1). The chain reactions of succinic acid provides for energy supply, essential for vital activity. Upon introduction of exogenous succinate, (Reamberin) the following effects are revealed: Direct action on metabolic processes in the cell — succinic acid catalyzes Krebs cycle by lowering concentration of lactate, pyruvate, and citrate, accumulated in cells during hypoxia. Effect on metabolic oxygen consumption (tissue hypoxia) — succinic acid improves cellular respiration by enhancing mitochondrial electron transport, increasing transmembrane proton influx, and reduction of nicotinamide adenine dinucleotide (NAD) dependent cellular respiration. Therapeutic action of Reamberin Apparent disintoxication effect, caused by improvement of metabolism, including enhanced detoxifying function of liver and stimulation of diuresis. Is based of the modification of metabolic and redox processes — cellular respiration, transport of ions and nutrients, synthesis of protein and adenosine triphosphate (ATP). Anti-hypoxic activity of Reamberin Is due to both the activation of succinate dehydrogenase system and the recovery of cytochrome oxidase, the key enzyme of mitochondrial electron transport chain. Anti-oxidative activity of Reamberin Is due to inhibition of mitochondrial peroxidase, restoration of superoxide dismutase activity, and enhancement of NAD-dependent enzymes activity, increase in reduced glutathione concentration.
- FINALIZATION OF CLINICAL trial DATA on efficacy of reaMberin
- One of the most efficient therapeutical approaches for patients in critical condition is the correction of intoxication syndrome. Study of the parameters of endogenous intoxication in patients at critical condition state has revealed, that administration of Reamberin in conjunction with intensive therapy results in a faster removal of endogenous toxic compounds from venous and arterial blood, thus attesting the restoration of metabolism in organs and tissues.
- All critically ill patients experience oxygen exchange disorders. The severity of the patient critical condition is determined by the extend of tissue hypoxia. This statement is true for the majority of ICU patients.
- Hypoxia induces the impairment of cellular homeostasis. Cellular energy depletion caused by hypoxia appears to be a triggering mechanism for many of the damaging biochemical processes (acidosis, increase in the phospholipase activity, lowered protein synthesis, etc) occurring during cell ischemia. Reamberin reduces tissue hypoxia at the expense of not only direct action, in other words as an energy substrate, but also at the expense of its effect on recovery of substantially disturbed oxygen utilization by tissues.
- Tissue hypoxia activates free radical generation and lipid peroxidation (LP), resulting in the damage of biological membranes. Reamberin reduces the intensity of LP, enhancing the adaptive capacity of cell membrane to extreme impacts.
- Current clinical data on Reamberin administration in hospitals show strong evidence of Reamberin high efficacy in treatment of acute poisoning, burn injury, surgical pathology, severe infectious diseases, complications caused by viral infections, and multiple organ failure of different origin. Such therapeutic approach abolishes the destructive effect of pathochemical cascades (such as LP, endotoxemia, etc.), induced by hypoxia. Clinical trials data on efficacy of Reamberin in intensive care of patients in critical condition prove the correctness of this statement.
- Administration of Reamberin to patients with acute poisoning is accompanied by the lowered intensity of central nervous system (CNS) depression, and by shortened duration of coma (from 55.5±9.5 h to 38.8±10.2 h) in particular. Faster recovery of the brain regulatory function resulted in a shortened stay of patients in ICU. Fast recovery of patients from life-threatening condition (from 97.2±15.2 h to 43.7±9.2 h) was registered. The frequencies of pulmonary complications as well as mortality rate were lowered from 48.3% to 26.2%, and from 24.1% to 10.8% correspondingly.
- Reamberin improves the functioning of liver, kidneys, and lungs. In the group of patients, who received Reamberin, a reduction in cytolytic enzymes (alanine aminotransferase and aspartate aminotransferase) as well as an improvement in the common laboratory blood values were recorded, thus reflecting the therapeutic action of Reamberin in general and indirectly attesting detoxifying and anti-oxidant properties of Reamberin (Fig.2).
- Administration of Reamberin during therapy of oxygen transport disorders results in positive dynamics of the respiratory, volume and tissue components of oxygen transport. Pulmonary gas exchange and metabolism were improved. Ultimately, all of the induced alterations resulted in reduction of intrapulmonary shunting part and increased oxygen capacity, which is a factor of increased oxygen delivery in tissues.
- Normalization of pulmonary gas exchange indices is associated with several mechanisms of action of Reamberin:
Firstly, Reamberin serves as an energy substrate, normalizing metabolism in pulmonary tissues during essential energy deficiency induced by hypoxia.
Secondly, Reamberin improves lung surfactant system state, which is the most susceptible to destructive changes due to hypoxia.
Thirdly, Reamberin protects lung tissue from damage, induced by activation of LP during reoxygenation.
Fourthly, Reamberin reduces the degree of endotoxin shock and recovers detoxification systems of the body (liver, kidneys), which results in decreased toxic load on the lungs.
- Development of new medicinal preparations aimed at acceleration of energy supply metabolic pathways is one of the goals in challenging hypoxic injury problems. Market appearance of Reamberin with succinic acid as an active principle meets these requirements within certain limits.
Reamberin, 1.5% solution for infusion is intended for use in pre-hospital treatment provided by the ambulance team, in the emergency room, in the ICU, and resuscitation unit. The main indication for Reamberin is presence of intoxication symptoms:
- Toxicological emergencies:
Acute lethal poisoning accompanied by sopor and coma;
Acute poisoning with hepatotoxic agents;
Acute poisoning with neurotoxic agents (including central nervous system (CNS) stimulants);
Withdrawal syndromes (alcohol, heroin);
Metabolic acidosis, alcoholic ketoacidosis;
Acute poisoning with prolonged exposure to toxic substances (more then 9 h following toxic exposure);
As a component of forced alkaline diuresis.
- Multiple organ failure (MOF)
- Burn injury
- Surgical pathology:
Sepsis (septicemia, septicopiemia)
In pre-treatment pharmacological procedure, before surgical intervention (pre-treatment strategies in thoracic surgery, vascular surgery, brain surgery also included);
In the schedule of post-surgical treatment plan of all complicated surgical interventions (such as peritonitis, necrotic pancreatitis, complicated cholecystitis, ileus etc.).
- Enteric infection (relief of intoxication symptoms)
- Viral hepatitis (relief of intoxication symptoms)
- Severe cases of pneumonia (relief of intoxication symptoms)
- Neuroinfections (relief of intoxication symptoms)
The efficacy of Reamberin is estimated on the basis of the laboratory and biochemical parameters monitoring, among them:
- hemoglobin concentration;
- erythrocytes counts and blood glucose level;
- blood gases, acid-base balance, and functional state of liver and kidneys.
Reamberin administration and simultaneous ventilatory support (ALV) should be performed under strict monitoring of acid-base balance and blood gases content. In case of hypo-oxygenation the oxygen flow rate should be increased to 5 L/min and more under continuous monitoring of acid-base balance and blood gases content.
- Toxicological emergencies:
- Inadequate efficacy of intensive care management efforts for oxygen delivery to tissues: decrease in partial pressure of arterial oxygen (below 60 mm Hg during artificial lung ventilation (ALV), permanent hypotension with gradient decrease in systolic blood pressure (below 70 mm Hg), marked anemia.
- Hypersensitivity to components of Reamberin.
- Apparent abnormal renal function (anuria).
- Hypoglycemia of different origin.
- ADVERSE REACTIONS
If given too fast the short-term blood-vessel reactions in forms of hyperemia and heat sensation can be developed.