RU2465829C1 - Method for assessing cerebral vessel responses in patients with arterial hypertension - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, neurology, neurosurgery and resuscitation. It involves transcranial Doppler sonography. It is followed by measuring a time-average mean blood velocity in medial cerebral artery and a concentration of carbon dioxide in expiratory air. Hypercapnic test with voluntary breath holding is conducted. Both hypercapnic test and rest parameters are evaluated. A cerebral value of blood autoregulation (CVBA) is calculated by formula. If the CVBA value >0.4 enables stating preserved cerebral autoregulation (CA), and the patient is referred to a low risk group of the CA disturbances. The value CVBA=0.3-0.4 indicates potential functional deterioration of cerebral circulation, a moderate risk of the CA disturbances. If observing CVBA<0.3, the patient is referred to a high risk group of the CA disturbances. The value CVBA<0 is considered to be an unfavourable prognostic sign specifying a very high risk of the CA disturbances.

EFFECT: method enables assessing cerebroprotective options of antihypertension treatment and a risk of disturbed cerebral vessel responses, thereby improving prevention of cerebrovascular arterial hypertension, as well as reducing a probability of undesired hypoperfusion effects of the hypotension therapy.

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Description

The invention relates to medicine, namely to cardiology, neurology, neurosurgery and resuscitation, and can be used to assess the reactivity of cerebral vessels in patients with arterial hypertension.

From the practice of medicine, a method is known for evaluating the autonomic tone and reactivity of cerebral vessels, which consists in determining the vasoconstrictor reserve for hypocapnic and vasodilation reserve for hypercapnic load with determining the peripheral resistance index and calculating the cerebral autonomic index (RF patent for the invention No. 2292844).

The disadvantages of this method are:

- inaccuracy of assessment due to the impossibility of standardizing the conditions for creating hypocapnia with the help of hyperventilation and hypercapnia with the help of breath holding;

- lack of consideration of the magnitude of systemic blood pressure.

A known method for assessing autoregulation of cerebral blood flow, according to which, during transcranial dopplerography (TCD), the linear blood flow velocity (LSC) and the diameter of the middle cerebral artery (SMA) are recorded at rest and against the background of inhalation with 100% oxygen for 2 minutes, the coefficient of change in blood flow velocity is calculated , autoregulatory response normalized to blood pressure (RF patent for the invention No. 2351282).

The disadvantages of this method are:

- a significant limitation of the use in medical practice, the possibility of undesirable effects during use, which is associated with the inhalation of 100% oxygen;

- lack of assessment of vasodilation reserve of cerebral blood flow.

A known method for assessing vascular cerebral reactivity is a prototype, which consists in assessing, according to the results of transcranial dopplerography, changes in the linear blood flow velocity in the middle cerebral artery during a hypercapnic test, calculating the coefficient of relative reactivity, which reflects the increase in peak systolic blood flow velocity in the SMA by 1% increase in carbon dioxide in alveolar air and is expressed as a percentage (RF patent for the invention No. 2365336).

However, this prototype has the following disadvantages:

- the lack of consideration of BFV at rest, that is, before applying hypercapnic exposure;

- the presence of a lower limit on the duration of the hypercapnic load (60 seconds), which can significantly limit the use of this method in some categories of the studied: elderly patients, patients with overweight, etc .;

- lack of consideration of the magnitude of systemic blood pressure.

The present invention is aimed at improving the prevention of cerebrovascular complications of hypertension.

The specified technical result is achieved by performing transcranial dopplerography, measuring the time-averaged average blood flow velocity in the middle cerebral artery and the concentration of carbon dioxide in the expired air, conducting a hypercapnic test with an arbitrary holding of breath, the parameters are evaluated both during a hypercapnic test and at rest , calculate the cerebral rate of blood flow autoregulation (CPAC) by the formula:

where Vcp ₁ - time-averaged average speed of blood flow of SMA at rest,

Vcp ₂ - time-averaged average blood flow velocity of SMA during a hypercapnic test,

pCO2 ₁ - carbon dioxide content in the exhaled air at rest (in mm Hg)

pCO2 ₂ - carbon dioxide content in exhaled air during a hypercapnic test (in mmHg)

GARDEN - systolic blood pressure,

DBP - diastolic blood pressure,

and with a CPAC value> 0.4, a conclusion is made about the preserved autoregulation of cerebral blood flow (AMA), the subject is classified as a low risk of AMA disorders, with a CPAC value of 0.3-0.4 indicate a possible deterioration in the functional state of cerebral circulation (moderate risk AMA disorders), with CPAA <0.3, the subject is classified as a high risk group for AMA disorders, CPAA value <0 is considered an unfavorable prognostic sign indicating a very high risk of AMA disorders.

The proposed method for assessing cerebral vascular reactivity in patients with arterial hypertension was successfully tested on 214 hypertensive patients who were outpatiently treated at the Healthcare Unit of Astrakhan in the period from 2007 to 2011, which were divided into 2 subgroups. The first subgroup included 79 patients with impaired hemodynamic response of SMA revealed at the beginning of the study during ventilation tests. The second subgroup included 135 patients without disturbances in the reactions of SMA during ventilation tests. CPAC was calculated both in the subgroups of hypertensive patients and in the comparison group (78 individuals without hypertension, comparable in the main clinical and demographic indicators with the examined patients). Given the presence in the CPAC formula of SBP and DBP, it is important that the compiled subgroups of patients did not significantly differ in the degree of increase in blood pressure. Fig. 1 shows the structure of the compared subgroups of patients with hypertension: the inner ring - the structure of the subgroup with impaired SMA reactions, the outer - with saved SMA reactions.

CPAC values were statistically significantly different in all groups. The maximum CPAC values were recorded in the comparison group. The distribution of CPAC in different groups of patients is presented in Fig. 2. (1 - comparison group (healthy volunteers), 2 - patients with hypertension with preserved reactions of SMA, 3 - patients with hypertension with impaired reactions of SMA).

CPA in patients with hypertension was 23% lower than in the comparison group (p = 0.03). The minimum CPAC values corresponded to the group of hypertensive patients with impaired hemodynamic response of SMA to the metabolic stimulus. The results of the statistical analysis show that CPAC can be used as a parameter evaluating the state of AMA.

Below are the results of testing.

Example 1. Patient Z. V.YU., 44 years old, suffers from hypertension for 11 years. Over the past year, he received combination therapy with enalapril and cardoflex with temporary improvement. At the time of the study, he complained of an increase in blood pressure, accompanied by moderate headache in the occipital region, weakness. Physical status without features. The examination revealed the following risk factors: male gender, family history, aggravated by hypertension, smoking, hypercholesterolemia (total cholesterol 6.35 mmol / l). HELL = 170/100 mm Hg Heart rate = 72 beats / min. When conducting TCD, the value of the time-averaged average blood flow velocity of MCA was at rest 51.3 cm / s, while conducting a hypercapnic test: 41.2 cm / s. During the test, the carbon dioxide content in exhaled air increased from 32 mm Hg. up to 34 mmHg CPAC was calculated by the formula:

CPAC = (Vcp ₂ -Vcp ₁ ) / (Vcp ₁ ∙ (pCO2 ₂ -pCO2 ₁ ) ∙ (GARDEN-DBP)) =

= (51.3-41.2) / (41.2 ∙ (34-32) ∙ (170-100)) = - 0.01

The calculation of CPAC showed a negative value of this indicator, on the basis of which the patient was assigned to a group of very high risk of AMA disorders. This is confirmed by the TCD results: a paradoxical reaction of SMA to hypercapnic load was recorded, signs of cerebral angioedema according to the hypotonic type, the value of the vasomotor reactivity index (IVMR) was 58.4.

After the combined antihypertensive therapy with bisoprolol and lisinopril, the target blood pressure values were not achieved; the blood pressure level was 150/90 mm Hg. Despite this, according to the results of a second study, the value of IVMR increased to 69.4, signs of cerebral angioedema were not recorded.

In accordance with the obtained values, the CPAC was re-calculated:

CPAC = (117.6-35.8) / (35.8 ∙ (30-29) ∙ (150-90)) = 0.38

Thus, the achieved level of blood pressure turned out to be optimal for the cerebral blood flow of a particular patient, as indicated by an increase in CPA to 0.38 (the patient from the very high-risk group moved to the moderate risk group for AMA disorders).

Example 2. Patient A.N.L., 51 years old, sick with hypertension for 7 years. A history of coronary heart disease. Angina pectoris. FC 2. I have not received regular antihypertensive therapy over the past year, and occasionally took andipal. He went to the doctor in connection with an increase in blood pressure, accompanied by stitching pains in the heart. When examining the lungs, vesicular breathing, no wheezing, NPV = 16 per min, the boundaries of relative cardiac dullness are not changed, heart sounds are clear rhythmic, heart rate = 68 beats / min, blood pressure 140/190 mm Hg When conducting TCD, the value of the time-averaged average blood flow velocity of SMA was at rest 47.2 cm / s, while conducting a hypercapnic test: 83.8 cm / s. During the test, the carbon dioxide content in the exhaled air increased from 31 mm Hg. up to 33 mmHg CPAC was calculated by the formula:

CPAC = (Vcp ₂ -Vcp ₁ ) / (Vcp ₁ ∙ (pCO2 ₂ -pCO2 ₁ ) ∙ (GARDEN-DBP)) =

= (83.8-47.2) / (47.2 ∙ (33-31) ∙ (140-90)) = 0.08

The patient was assigned to a high-risk group for AMA disorders. In the study of the reactivity of SMA, signs of hypodonic type of angioedema were detected, the registered dynamics of peripheral resistance indices indicated signs of an emerging vasodilation deficiency of SMA, and the IVMR was 23.4.

Against the background of amlodipine monotherapy, the target blood pressure values were achieved: BP = 130/85 mm Hg, an increase in IVMR to 43.4 was recorded, equalization of the amplitudes of the MCA reactions during ventilation tests - the disappearance of signs of cerebral angioedema. In accordance with the obtained values, the CPAC was re-calculated:

CPAC = (111.3-38.1) / (38.1 ∙ (34-33) ∙ (130-85)) = 0.43

An increase in CPAC to 0.43 allowed the patient to be assigned to the low-risk group for AMC disorders, which makes it possible to consider the decrease in blood pressure to target values appropriate from the standpoint of the effect on a particular patient’s cerebral blood flow.

Example 3. Patient K.V.N., 51 years old, increased blood pressure over 8 years. Atenolol was taken before the study. I went to the doctor due to the lack of effect of the received treatment. During a physical examination, attention was paid to a shift of the left border of relative cardiac dullness 2 cm outward from the left mid-clavicular line, heart rate = 72 beats / min, blood pressure = 180/100 mm Hg. Hypertrophy of the left ventricular myocardium was confirmed by echocardioscopy (left ventricular myocardial wall thickness 12 mm), and laboratory examination revealed hypercholesterolemia (total cholesterol 6.3 mmol / L). At the initial visit, the value of the time-averaged average blood flow velocity of SMA during TCD was at rest 49.7 cm / s, during the hypercapnic test: 192.3 cm / s. When performing the test, the carbon dioxide content in exhaled air increased from 31 mm RT .art. up to 35 mmHg CPAC was calculated by the formula: CPAC = (Vcp ₂ -Vcp ₁ ) / (Vcp ₁ ∙ (pCO2 ₂ -pCO2 ₁ ) ∙ (SAD-DAD)) = (192.3-49.7) / (49.7 ∙ (35-31) ∙ (180-100)) = 0.1.

Based on the obtained CPAC value, the patient was assigned to the high risk group for the development of AMA. A study of cerebrovascular reactivity showed the presence of signs of hypertensive angioedema.

On the background of bisoprolol monotherapy, blood pressure decreased to 125/85 mm Hg. Conducting ventilation tests with TCD showed a transformation of the amplitudes of the hemodynamic reactions of SMA to a metabolic stimulus - if the signs of cerebral angioedema were initially determined by the hypertonic type, then, after active antihypertensive therapy, hypothonic type of angioedema began to be recorded, indicating a sharp depletion of the reserve of SMA to vasodilation. In accordance with the obtained values, the CPAC was re-calculated:

CPAC = (146.8-92.3) / (92.3 ∙ (34-33) ∙ (125-85)) = 0.15

CPAC, although it increased to 0.15, however, did not allow changing the patient's risk group. The insufficient increase in CPAC indicates that the achievement of target blood pressure values in this patient led to a violation of AMA, which can lead to the formation of acute or chronic hypoxia of the brain.

These clinical examples demonstrate that the clinical use of CPAC makes it possible to determine the level of blood pressure adapted to the individual needs of the cerebral blood flow of a particular patient with hypertension, which significantly reduces the risk of hypoperfusion complications of antihypertensive therapy.

The proposed method achieves an assessment of the cerebroprotective potential of antihypertensive treatment and the risk of impaired cerebrovascular reactivity, which improves the prevention of cerebrovascular complications of hypertension, reduces the likelihood of undesirable hypoperfusion effects of antihypertensive therapy.

Claims (1)

A method for assessing cerebral vascular reactivity in patients with arterial hypertension, including transcranial dopplerography with a linear blood flow velocity measurement in the middle cerebral artery and measuring carbon dioxide in exhaled air, characterized in that the time-averaged average blood flow velocity is measured, a hypercapnic test with an arbitrary delay respiration, the parameters are evaluated both during the hypercapnic test and at rest, then the cerebral index is calculated spruce blood flow autoregulation (CPAC) according to the formula

where Vcp ₁ - time-averaged average velocity of blood flow of SMA at rest;
Vcp ₂ - time-averaged average blood flow velocity of SMA during a hypercapnic test;
pCO2 ₁ - carbon dioxide content in the exhaled air at rest, mm Hg;
pCO2 ₂ - carbon dioxide content in exhaled air during a hypercapnic test, mmHg;
GARDEN - systolic blood pressure;
DBP - diastolic blood pressure,
and with a CPAC value> 0.4, a conclusion is made about the preserved autoregulation of cerebral blood flow (AMA), the subject is classified as a low risk of AMA disorders, with a CPAC value of 0.3-0.4 indicate a possible deterioration in the functional state of cerebral circulation - moderate risk AMA disorders, with CPAA <0.3, the subject is classified as a high risk group for AMA disorders, CPAA value <0 is considered an unfavorable prognostic sign indicating a very high risk of AMA disorders.

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