Cranial cerebral trauma brain edema

State Scientific and Clinical Center for Miner Health Protection

The invention relates to the field of medicine, andnamely to intensive therapy and neurosurgery, and can be used to treat progressive cerebral edema resulting from severe craniocerebral trauma (TCMT).
Results of intensive carepost-traumatic swelling of cerebral swelling continue to be unsatisfactory, which makes it necessary to study and search for new methods of treating this pathological condition.
An extremely important mechanism is associated with the damaging role of excess concentrations of intracellular Ca2 + and the release of arachidonic acid (AA) from the composition of phospholipids of biomembranes.
Overloading neurons with Ca ions2 + leads to the activation of phospholipase A2, due towhich cleaves polyunsaturated AA from the position in the molecules of phospholipids (Lazarewich J. W. Salinska E. Vroblewski J.T. // Ibid. - P 55 - 61). Subsequent transformations of AA under the action of cyclooxygenase lead to the formation of a whole family of biologically active compounds (prostaglandins, thromboxanes) that contribute to the development of inflammatory phenomena in trauma, and the process of its transformation into hydroxy-, hydroperoxyforms and leukotrienes is associated with the generation of free radicals (Chan PH Fishman RA Longar S. et al., Prog Brain Res., 1985, Vol 63, P. 227-235). Thus, the mechanisms of activation of lipid peroxidation in the brain are diverse in trauma.
In a significant part of the work devoted to thisaspect of the pathogenesis of CCT, the value of free radicals in the "damage" of the brain in trauma is confirmed by the therapeutic efficacy of various antioxidants and blockers of the incoming calcium current (Nair S. Springer, J. Robine V et al., International Neuro-trauma Symposium, 2-nd .- Glasgow , 1993. - P. 34, Pulsinelli W. Cho S / International Neurotrauma Symposium, 2-nd. - Glasgow, 1993. - P. 49).
Prostaglandins actively influence microcirculation,have a multidirectional effect on the aggregate state of thrombocytes and erythrocytes, the permeability of capillaries for plasma, water. Provoke the occurrence of interstitial edema, disruption of adaptive reactions of the brain to damage, the spread of necrosis to the border zone of brain damage (bruise).
Vascular spasm of the arterial circle of the brain isa frequent complication. It is believed that this process is caused by the contact of extravasal blood with the outer shell of the brain vessels and is mediated by prostaglandins (PG). This hypothesis was tested on an isolated preparation of the arterial circle of the dog's large brain, perfused at a constant flow and pressure at the entrance. Local application of blood to the external surface of the vessels caused an increase in the inlet pressure by an average of 16.6 ± 1.8 mm Hg. This reaction could be prevented by one of four structurally different cyclooxygenase inhibitors: acetylsalicylic acid, indomethacin, ibuprofen; consequently, an increase in vascular resistance is mediated by PG. Arachidonic acid, PGE2 and PG2α also caused vasoconstriction. The experimental data obtained demonstrate the ability of cerebral vessels to synthesize vasoconstrictor substances of PG and to react to known vasoactive PG (Lang S. A. Maron M. 1988).
Currently used various schemesconservative intensive therapy of developing and progressive cerebral edema, unfortunately, do not solve all the problems, and sometimes create conditions for aggravating the resulting pathophysiological disturbances (Ward JD Choi S. 1989 Mendelow AD Teasdale JM Russel T. et al., 1985 Mize Laar JP , Luntz HA, et al 1984, Braakman R, Schouten HSA, et al 1983, Lanier WL, 1991).
Because prostaglandins are involved in the processthere is evidence of the benefits of using prostaglandin inhibitors in the treatment of severe craniocerebral trauma (Milde, LN 1990, Murdoch J. Hall R. 1990, Ping F. C. Jenkins, L. C. 1978).
Known method of complex intensive therapyprogressive edema of the brain, including prolonged artificial ventilation of the lungs including with moderate hyperventilation, sedation aimed at creating a deep medical sleep of the patient, anesthesia, the use of spasmolytic agents, diuretics (furosemide), manitol, hormones (Neurotraumatology / Ed. Konovalova, LB Likhterman, AA Potapova - VIC-FERRO, Moscow, 1994), which allows to carry out therapeutic measures aimed at correction of intracranial volumes due to reduction of cytogenic and vasogenic th part of the edema. This method has drawbacks:
- in the following scheme of complex intensive therapy, all links of the pathophysiological mechanism of cerebral edema development are not sufficiently taken into account,
- focusing only on changes in intracranialvolumes and associated clinic. manifestations of progressive cerebral edema, therapy is delayed and takes a har-r symptomatic, rather than pathogenetic.
The closest way to the claimeda method for the treatment of cerebral circulation disorders that occurs immediately after the craniocerebral trauma associated with the formation of microthrombi and stasis, including artificial ventilation, anesthesia and sedation with narcotic analgesics and beanzediazepines, GHB, myoplegia, myoreclaxants, intravenous infusion of standard crystalloid infusion media, and nutritional support. The basis of infusate is the isotonic solution of sodium chloride, Ringer-Locka, or 5% of Glucose. Constant components are novocaine and heparin. Of the other drugs, dentine is often injected. With high intracranial pressure, stagnant stasis on the fundus, after exclusion of the hematoma, administer mannitol in a dose of up to 0.5 g per 1 kg of body weight. To improve the microcirculation, rheopolyglucin (400.0) is separately administered. The average duration of infusion is 7 days (MG Drulyuk, NS Drulyuk, Intraarterial Infusion with CCT (AI). // Neurotraumatology. / Edited by AN Konovalov, LB Likhterman, AA Potapova , Moscow, IPC "VAZAR-FERRO", 1994, pp. 81-82).
However, this method is not without its shortcomings:
- the use of heparin in infusion as a direct anticoagulant can lead to recurrence of intracranial hematomas, intracerebral hemorrhages with worsening of patients,
- the use of eufillina is unreasonable in connection with the development of the syndrome of stealing blood flow in the area of ​​damage to the brain tissue in comparison with the intact,
- the use of relatively large volumes of infusion media against the background of the existing cerebral edema may lead to its further aggravation,
- this therapy is not pathogenic, but is more symptomatic
The object of the present invention is to increaseeffectiveness of treatment and reduction of cerebral edema by inhibiting cyclooxygenase synthesis of prostaglandins from arachidonic acid in early treatment.
The task is achieved by the fact that additionally,simultaneously with the standard therapy, the first day, the infusion of aspizole into the internal carotid artery, at a therapeutic dose of 1000 mg of aspizol dissolved in 50 ml of saline at a rate of 0.3472 mg per minute continuously, while the duration of administration is 10-14 days .
Novelty of the method:
1. Aspisol (Aspisol) -D, L-lysine mono (acetylsalicylate) is manufactured by Bayer, (injectable form of acetylsalicylic acid: indicated for the treatment of pain, fever, rheumatic diseases, neuritis, surface vein thrombophlebitis, postoperative thrombosis and embolism Register of medicines in Russia, fifth edition // edited by Yu.F. Krylova, Moscow, "REMACO", 1997/1998)) - makes it possible to block the enzyme cyclooxygenase, interrupting the synthesis of cyclic endoperoxides (PGG2. PGH2), and then prostaglandins (PGE2, PGF and others), prostacyclin, thromboxane A2. it is the relationship of the last two, withcraniocerebral trauma, determines the course of the pathological process. Aspizol, blocking the cyclooxygenase of platelets, erythrocytes, the vascular wall, leads to a decrease in aggregation of blood cells, vasodilation, thereby creating the prerequisite for the restoration of impaired microcirculation and the aggregate state of the blood. At the same time, the cyclooxygenase of the vessels restores its activity for several hours, and the inhibiting effect on platelets persists for the entire period of its life, which is 7-10 days. The dose of aspizol was selected in vitro, the ability to induce the aggregation capacity of platelets and erythrocytes was the determining factor. The selected dose was 1000 mg of aspizol (500 mg of acetylsalicylic acid) and is reliable in changing the aggregation properties of erythrocytes and platelets.
2. The introduction of aspizol against the background of standard therapy of patients with severe craniocerebral trauma with the phenomena of cerebral edema provides a reduction in the increase in the phenomena of cerebral edema, an earlier restoration of the metabolic functions of the brain and as a consequence an early regress of the neurological deficit, a decrease in the lethality of this category of patients from the progressive edema of the head the brain.
The method was carried out as follows.
When a patient with severecraniocerebral trauma, in an acute period accompanied by cerebral edema, in the intensive care unit, patients underwent or did not undergo surgical treatment for intracranial hematomas, performed artificial ventilation, sedation and analgesia with narcotic analgesics: promedol up to 80-100 mg / day, diazepam up to 40 mg / day, GHB 20% to 30 g / day, myoplegia by arduan up to 12 mg / day, antibacterial therapy: antibiotics of the group of synthetic penicillins and aminoglycosides in recommended daily allowances up to Infusion therapy with NaCl solution 0,9% and Ringer-Locka solution at the rate of 40-50 ml / kg / day, correction of electrolyte disturbances of KCl of 7.5% and MgCl 25% in recommended amounts of mmol / kg / day, systemic application heparin in 10 thousand units / day, disaggregants: trental up to 5 ml / day, low molecular weight dextrans in the first 2 days: rheopolyglucose 400 ml / day, nutritional support was provided by enteral probe feeding. Standard therapy is carried out for the entire duration of the acute and subacute period of the course of craniocerebral trauma and is 21-30 days.
Retrograde catheterization of the internalbranches of the carotid artery by a plastic catheter with a diameter of 0.6 mm from the side of the greatest damage to the brain. On the first day and simultaneously with the standard therapy, the administration of aspizol was carried out with a syringe infusomat, which allowed the drug to be administered for a long time during the entire treatment period. Aspizol was dissolved in 50 ml of physiological solution, the final concentration of aspizol in the solution is not of fundamental importance, since the drug is administered at a constant rate of 0.3472 mg per minute. The duration of therapy was determined by the clinical state, the dynamics of biochemical processes, the dynamics of saturation of the brain tissue with water according to impedanceometry, computer tomography of the brain, was from 10 to 14 days, the course of an acute period of craniocerebral trauma.
Example. Patient K. 50 years old, was taken to the neurosurgical department of the clinic 1 hour after a severe craniocerebral trauma. Diagnosis: Severe closed craniocerebral trauma, severe hemorrhoid bruise of the brain mainly of the basal parts of the frontal lobes, massive subarachnoid hemorrhage. Swelling of the brain in the subcompensation stage.
Upon admission, the condition is severe due tosevere brain contusion. The level of impairment of consciousness on a scale Glasgow com 8 points. Within 1 day was treated in the neurosurgery department. The condition progressively worsened due to an increase in cerebral edema and the appearance of dislocation syndrome, the level of impairment of consciousness was 5 on the Glasgow scale. In this regard, transferred to the intensive care unit, the operation was performed: the imposition of a milling hole in the left frontal region, the removal of lamellar subdural hematoma. Osseous resection trepanation in the frontal area, right, removal of intracerebral hematoma, contusion area.
In the early postoperative period on the backgroundcarried out standard therapy, including mechanical ventilation, infusion therapy, antispasmodics, catheterization of the internal branch of the right carotid artery was carried out, aspizol was infused by the proposed method.
By 5-7 days regression of neurologicalsymptoms, increased levels of consciousness up to 8 on the Glasgow scale, restoration of spontaneous breathing, weaning of the patient from the ventilator and extubation.
A positive change is observed at the same time.according to biochemical indices of blood flowing from the brain with the restoration of glucose and oxygen consumption, a decrease in the level of lipid peroxidation production. By impedance, there is a decrease in cellular and interstitial cerebral edema. According to CT, moderate positive dynamics of hemorrhagic contusion of the frontal lobes occurs with resorption of hematomas. Edema of the frontal lobes. Reducing the focus of injury. Regression of dislocation syndrome.
Intra-arterial infusion was carried out for 10 days. On the 11th day the patient was transferred to the specialized department.
The proposed method is applied in 14 patients with severe traumatic brain injury.
The proposed method allows to reduce the probabilityprogression of cerebral edema. Thus, there is a reduction in the increase in the phenomena of brain edema, an earlier restoration of metabolic functions of the brain and, as a consequence, an early regression of the neurological deficit, a decrease in the mortality rate of this category of patients from the progression of brain edema.

A method for the treatment of cerebral edema in patients withtraumatic brain injury, including artificial lung ventilation, pain relief and sedation with narcotic analgesics and bean cediazepines, GHB, muscle relaxant myoplegia, intravenous infusion of standard crystalloid infusion media, nutritional support, differing from the same infusion of aspizol into the internal carotid artery at a therapeutic dose of 1000 mg of aspizol dissolved in 50 ml of physiological saline, with soon 0.3472 mg / min continuously, with the duration of the introduction of 10 - 14 days.