RU2809915C1 - Method of detecting septic encephalopathy by recording evoked potentials - Google Patents

Abstract

FIELD: medicine; resuscitation.

SUBSTANCE: invention can be used for the treatment of septic encephalopathy in the acute period. Multimodal evoked potentials (EPs) are recorded on the first day after the diagnosis of sepsis. The latency of peaks N9, N13, N20 and interpeak intervals N9-N20 are determined using somatosensory evoked potentials with a stimulus frequency of 20.0 mA and a stimulus duration of 0.1 ms. The latency indicators of the N1, P2, N2 peaks are determined using visual EPs with a stimulus in the form of a flash of light with a stimulus duration of 10–20 ms. The latency indicators of peaks I, III, V are determined using acoustic EPs with a stimulus of ±100 dB SPL with a stimulus duration of 0.1 ms. If there are deviations in the obtained EP indicators from the normative indicators towards an increase or decrease in at least one of the specified types of EP, septic encephalopathy is detected.

EFFECT: method provides increased efficiency of early detection of septic encephalopathy.

1 cl, 6 dwg, 16 tbl, 2 ex

Description

The invention relates to medicine, in particular to resuscitation, and can be used to detect septic encephalopathy in the early period (subclinically).

The lack of specific methods for detecting septic encephalopathy complicates the diagnosis (Gofton T.E., Young G.B. Sepsis-associated encephalopathy. Nat Rev Neurol 2012; 8: 557-566. doi:10.1038/nrneurol.2012.183).

Evoked potentials are electrical activity generated in response to a sensory or motor stimulus. Measurements of evoked responses can be made at various points along the neural pathway involved in their generation.

There are types of evoked potentials (EP) depending on the exogenous stimulus: visual evoked potentials (VEP), auditory evoked potentials (ASEP), somatosensory evoked potentials (SSEP) (Evoked potentials: a guide for doctors - Toropina G.G. 2016)

Somatosensory evoked potentials (SSEPs) are bioelectrical oscillations that occur in nerve structures in response to external stimuli and reflect the conduction of an afferent wave along the proprioceptive pathways, which allows one to obtain information about their integrity or damage at a certain level, and in the early stages of the pathological process. In practical diagnostics, only electrical stimulation of peripheral nerves (nn.medianus, ulnaris, tibialis) is used.

Somatosensory evoked potentials can be determined from three levels:

1. peripheral nerve trunks - electrodes are installed over the nerve trunk being studied - Erb's point (ipsi- and contralateral side) when stimulating the nerves of the arm and the popliteal fossa / head of the fibula when stimulating the nerves of the leg. Components P8, N9 are recorded during stimulation of the upper limbs, and FP-R during stimulation of the lower limbs.

2. cervical and lumbar enlargements of the spinal cord - when recording from the cervical enlargement, the recording electrode is installed at the level of the spinous process of the CVII vertebra, the reference electrode is 6 cm higher or at point Fz; in this case, components N11, N13 are isolated;

When recording EP from the level of the lumbar enlargement, the recording electrode is placed above the LIII vertebra, the reference electrode is 6 cm higher; when recording, responses N22, P23 are highlighted;

3. cranial lead - to record cortical responses, electrodes in leads C3/C4 are used, the scalp electrode Fz is used as a reference electrode; when stimulating the nerves of the upper extremities, the N20 response is recorded; when stimulating the nerves of the lower extremities, the P45 component is identified.

It is generally accepted that somatosensory evoked potentials reflect the conduction of the afferent impulse predominantly through the posterior cords of the spinal cord, the brain stem and thalamocortical pathways into the cerebral cortex (Gnezditsky V.V. Evoked potentials of the brain in clinical practice. Taganrog: Publishing House TRTU; 1997; 258 s).

Visual evoked potentials (VEPs) are a method that examines conduction along the visual pathway from the retina to the visual cortex. Stimulation is carried out with a reverse checkerboard pattern, with a pronounced decrease in visual afferentation - with a flash of light.

The generator of the main component of evoked potentials is located in the occipital cortex, but its characteristics can change due to a lesion in any part of the optical path. As a rule, peaks N75, P100, N145 (for a reverse checkerboard pattern) or N1, P1, N2, P2 (for a flash of light) are identified.

Acoustic brainstem evoked potentials (ASEP) are a method for assessing conduction in the auditory nerve, auditory pontine nuclei and midbrain. ASVP is the only method that allows one to assess the functional state of the structures of the pontomedullary and pontomesencephalic levels of the brain.

Septic encephalopathy is an early manifestation of systemic infection, when the source of infection is outside the central nervous system (CNS), but the systemic inflammatory response causes organ dysfunction, including the brain; the basis of this dysfunction (or acute cerebral failure) is pathophysiological processes that reflect mechanisms of damage to the blood-brain barrier, brain cells - microglia, which perform the function of immunocompetent cells in the central nervous system in the form of their activation, increased levels of pro-inflammatory cytokines in the cerebrospinal fluid and medulla, which is the essence of neuroinflammation and leads to reversible or irreversible damage to neurons, their trophism, groups of neurons in the form of nuclei of the autonomic nervous system in the brain stem, in the cerebral cortex, in the subcortical nuclei.

Multimodal EPs are objective diagnostic methods that demonstrate the level and degree of conduction disturbances in brain structures, and can complement clinical examination in certain groups of patients in critical condition, for example, after anoxic brain injury (Oddo M, Rossetti AO: Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia. Crit Care Med. 2014, 42: 1340-1347. 10.1097/CCM.0000000000000211).

Some authors have conducted studies of somatosensory evoked potentials in patients with dyscirculatory encephalopathy, suggesting that the cause of non-systemic dizziness in them is a lack of function of the proprioceptive sensory stabilizing system at the cerebral level (T.A. Davydova, A.V. Gustov, K.M. Belyakov. Somatosensory evoked potentials in the diagnosis of non-systemic dizziness. STM, 2010 - 4, p. 111.)

There is a known method of using somatosensory evoked potentials in miners in vibration-hazardous professions, which makes it possible to identify subclinical slowing of the afferent excitation wave in the conduction system, and for the purpose of early detection of signs of cognitive impairment, the use of cognitive evoked potentials can be recommended (Vasilieva L.S., Rusanova D.V. , Slivnitsyna N.V., Lakhman O.L. Features of damage to the nervous system revealed by recording somatosensory evoked potentials in patients with vibration disease. Hygiene and Sanitation. Volume 99, 2020, p. 1074).

The known diagnostic method allows us to identify subclinical manifestations of vibration disease.

There is also a known method for diagnosing damage to the brachial nerve ganglion. Upper extremity SSEP analysis can be used to determine the extent and location of the lesion. In particular, differentiation is possible between lesions proximal or distal to the dorsal root ganglion. Additional information about damage to the spinal cord roots can be obtained from a comparison of the responses of the radial (CVIII and T1) and median (CVI and CVII) nerves (Zenkov et al., 1991; Liverson and Dong, 1992).

There is also a known method for neurological monitoring in patients on extracorporeal membrane oxygenation (ECMO). In a prospective study, neurological complications were found in 85% of patients treated with SSEP. 70% had unfavorable outcomes. SSEPs have demonstrated the ability to predict neurological outcome (Sung-Min Cho, Wendy Ziai, Yunis Mayasi, Aaron M Gusdon, Jennifer Creed, Matthew Sharrock. Noninvasive Neurological Monitoring in Extracorporeal Membrane Oxygenation. 2020. DOI: 10.1097/MAT.0000000000001013).

From the known analogues, as a prototype for the claimed method, a method of using somatosensory evoked potentials in miners in vibration-hazardous professions was selected, which makes it possible to identify a subclinical slowdown in the conduction of the afferent excitation wave in the conduction system (Vasilieva L.S., Rusanova D.V., Slivnitsyna N.V., Lakhman O.L. Features of damage to the nervous system revealed by recording somatosensory evoked potentials in patients with vibration disease. Hygiene and Sanitation. Volume 99, 2020, p. 1074).

The problem solved when creating the claimed invention is the early detection of septic encephalopathy.

The resulting technical result of the claimed invention is to increase the efficiency of early detection of septic encephalopathy and the possibility of initiating early treatment.

The technical result is achieved due to the fact that in the method for detecting septic encephalopathy by recording evoked potentials, including registration of multimodal evoked potentials (EP) on the first day from the moment of diagnosis of sepsis, according to the invention, the latency of peaks N9, N13, N20 and inter-peak intervals N9 are determined -N20 using somatosensory evoked potentials with a stimulus frequency of 20.0 mA, and a stimulus duration of 0.1 ms; peaks N1, P2, N2 using visual EPs, with a stimulus in the form of a flash of light, stimulus duration 10-20 ms; and peaks I, III, V using acoustic EPs with a stimulus of ±100 dB SPL, stimulus duration of 0.1 ms; if there are deviations in the obtained EP indicators from the normative indicators towards an increase or decrease in at least one of the specified types of EP, septic encephalopathy is detected. Data is evaluated in the following units:

1. latency and interpeak intervals in ms;

2. amplitude in µV.

The proposed method for identifying septic encephalopathy by registering CAP allows one to verify sepsis-associated encephalopathy, begin timely treatment, improve cognitive function and overall outcome.

The claimed method provides illustrations explaining clinical examples 1 and 2, where:

in fig. 1 - shows a graph of short-latency somatosensory EPs when recorded on the 1st day from the moment of diagnosis of sepsis. Stimulation n. medianus on the right (A), stimulation n. medianus on the left (B); leads Ср3-Fpz, on the right Ср3-Erb, on the left Ср3-Erb (clinical example 1);

in fig. 2 - shows a graph of short-latency (stem) auditory EPs on the 1st day from the moment of diagnosis of sepsis: stimulation on the right (A), stimulation on the left (B). Leads Cz-M1; Cz-M2 (clinical example 1);

in fig. 3 - graph of visual EPs for a flash, registration on the 1st day from the moment of diagnosis of sepsis. Leads O1-Fz; O2-Fz (clinical example 1);

in fig. 4. - graph of short-latency somatosensory EPs when registered on the 1st day from the moment of diagnosis of sepsis. Leads Ср3-Fpz, Ср3-Erb, (clinical example 2);

in fig. 5 - graph of short-latency (stem) auditory EPs when recorded on the 1st day after the diagnosis of sepsis: stimulation on the right (A), stimulation on the left (B). Leads Cz-M1; Cz-M2. (clinical example 2);

in fig. 6 - graph of visual EPs for a flash, registration on the 1st day from the moment of diagnosis of sepsis. Leads O1-Fz; O2-Fz. The method is carried out as follows:

When diagnosing sepsis, the patient undergoes EP registration on the first day: somatosensory, acoustic, visual in order to identify sepsis-associated encephalopathy.

The conduction time of a nerve impulse is assessed along the entire nerve path: from peripheral to cortical (latency, ms), multiple stimulation and sequential averaging are used.

1) short-latency SSEPs upon stimulation of the nn.medianus (ulnaris) on both hands - cortical, segmental and neural EPs were recorded;

2) ASEP to stimulus 80 dB monaural stimulation;

3) VEP for a flash of light with a duration of 10 ms.

To record SSEPs in response to median nerve stimulation, recording electrodes were placed at Erb's point, just above the midpoint of the clavicle, above the brachial plexus. The next electrode was placed in the midline on the back of the neck at the level of the second cervical vertebra, relatively close to the dorsal column nuclei. The signals recorded here indicated proper transmission of the response from the peripheral nervous system to the spinal cord and rostrally through the spinal cord into the medulla oblongata. The final electrodes were placed on the scalp over the sensory (parietal) cortex, contralateral to the stimulated limb. The signals recorded here verify the integrity of the pathway through the brainstem, thalamus, and internal capsule and can be used in assessing the adequacy of cerebral blood flow in a given cortical area. Peak-to-peak latencies were also determined to estimate relative conduction times, such as conduction times from N9 to N13, reflecting the time of transmission from the brachial plexus to the brainstem, or conduction times from N13 to N20, reflecting the time of transmission between the dorsal column nuclei and the primary sensory bark

Evaluation of EP parameters of all modalities is carried out according to standard protocols. Deviations from the normative parameters of latency, interpeak intervals and amplitude are taken as evaluation signs (Gnezditsky V.V., Evoked brain potentials in clinical practice. - Taganrog: TRTU Publishing House-1997, - 49 p.: ISBN 5-230-24743-6 .).

The following clinical examples illustrate the possibility of early detection of septic encephalopathy after the diagnosis of sepsis.

Example 1. Patient P., 64 years old, with a main diagnosis of coronary heart disease

On November 22, 2022, a planned surgical intervention was performed: mammary coronary bypass grafting of the anterior interventricular artery and circumflex artery on a beating heart. Eversion carotid endatherectomy on the right.

The postoperative period was complicated by acute disruption of mesenteric circulation with the development of peritonitis and sepsis. On November 26, 2022, diagnostic laparoscopy and laparotomy were performed. Left-sided hemicolectomy, sanitation, drainage of the abdominal cavity. Formation of transversostomy. Angioplasty with stenting of the common iliac artery (CIA), external iliac artery (EIA) and superficial femoral artery (SFA) on the right.

The patient had a number of concomitant diseases: type 2 diabetes mellitus. Chronic gastritis, without exacerbation. Hypertension stage III. Risk of cardiovascular complications 4. Nephropathy of mixed origin (diabetic, hypertensive). High values of laboratory markers of systemic inflammation were recorded: CRP - 295 mg/l; leukocytosis in a clinical blood test - 18 * 10/9 g/l; shift of the leukocyte formula to the left. A quantitative method for determining the level of procalcitonin showed a value of 8.49 ng/ml. Unstable hemodynamics with a tendency to arterial hypotension up to 80/50 mm Hg were noted. requiring the use of vasopressor support with norepinephrine. Confusion and hypoactive delirium were detected according to a neurological examination using the GCS, RASS, CAM-ICU scales.

When studying SSEPs from the upper limbs (n.medianus stimulation), we obtained neural, segmental and cortical EPs with stimulation on both sides. The amplitude of neural and spinal EPs was reduced, the interpeak interval N9-N20 increased on the right by 30-38%, on the left by 26.5-33%, which can be observed when conduction along the somatosensory pathway is slowed on both sides and corresponds to conduction disturbances on the spinothalamic level of the somatosensory pathway on both sides with slight asymmetry (Fig. 1 A, B; Tables 1, 2, 3).

When studying ASVP, all the main peaks were visualized; an increase in the interpeak interval III-V on the right by 30% was observed without an increase in the main interval I-V, which may correspond to a slowdown in conduction at the ponto-mesencephalic level of the brain stem on the right (Fig. 2 A, B; Table 4 , 5, 6, 7).

Table 4 - ASVP latencies when registered on the 1st day from the moment of diagnosis of sepsis.

VEPs were examined for a flash of light, recorded on both sides, an increase in the latencies of P1, N2 on the left and N2 on the right was noted, which may correspond to a partial disruption of non-specific visual afferentation (Fig. 3; Tables 8, 9).

When assessing these values, sepsis-associated encephalopathy was identified. Thus, it was found that the neuromonitoring modalities used to clarify the degree of damage to the nervous system demonstrated early changes in the subcortical (N13-N20) and cortical (N20-N70) SSEP and VEP pathways, which allows us to consider the EP recording method as specific for identifying SAE in sedated patients in critical condition.

Example 2. Patient S., 74 years old, with a main diagnosis of coronary heart disease.

On November 23, 2022, a planned surgical intervention was performed - extended right-sided hemicolectomy with lymphadenectomy for poorly differentiated adenocarcinoma of the cecum, highly differentiated adenocarcinoma of the ascending colon. The postoperative period was complicated by acute disruption of mesenteric circulation with the development of peritonitis and sepsis. On November 27, 2022, relaparotomy, revision of the abdominal organs, resection of transversoileoanastamosis, resection of the small intestine, formation of an ileostomy, sanitation and drainage of the abdominal cavity were performed.

The patient had a number of concomitant diseases: coronary heart disease. Chronic gastritis, without exacerbation. Hypertension stage III. Risk of cardiovascular complications 4. Severe chronic anemia. Previous thrombophlebitis, complete recanalization. High values of laboratory markers of systemic inflammation were recorded: CRP - 306 mg/l; leukocytosis in a clinical blood test - 21 * 10/9 g/l; shift of the leukocyte formula to the left. A quantitative method for determining the level of procalcitonin showed a value of 45.2 ng/ml. Unstable hemodynamics with a tendency to arterial hypotension up to 76/50 mm Hg were noted. requiring the use of vasopressor support with norepinephrine. Impaired consciousness in the form of stupor was detected according to a neurological examination using GCS scales.

A study of multimodal EP was conducted on the 1st day after the diagnosis of sepsis. When studying SSEPs - recorded on both sides - the EP amplitude is S>D, the N9-N20 interval on the right is increased by 38%, on the left by 26.5%), which corresponds to a conduction disorder at the spinothalamic level of the somatosensory pathway on both sides S<D . (Fig. 4; Table 10, 11, 12).

When studying ASVP, the peaks are poorly identified; only peak I (auditory nucleus) is recorded on the right, which corresponds to a complete disruption of conduction along the brain stem starting from the caudal level. (Fig. 5 A. B; Tables 13, 14).

VEPs were examined for a flash of light, recorded on both sides, the latency of the N2 peak on both sides was increased, more on the right, the amplitude of the EP S>D by 70%. Visual afferentation is preserved, better on the left. (Fig 6; table 15, 16).

When assessing these values, sepsis-associated encephalopathy was identified. Thus, it was found that the neuromonitoring modalities used to clarify the degree of damage to the nervous system demonstrated early changes in the subcortical (N13-N20) and cortical (N20-N70) SSEP and ASEP pathways, which allows us to consider the method of recording EPs as specific for identifying SAE. It can be concluded that detection of SAE at the subclinical stage is possible by recording SSEP, VEP and ASEP in the early stages of the disease.

Claims (1)

A method for detecting septic encephalopathy by recording evoked potentials, including recording multimodal evoked potentials(EP) on the first day after the diagnosis of sepsis, characterized in that the latency of peaks N9, N13, N20 and interpeak intervals N9-N20 are determined using somatosensory evoked potentials with a stimulus frequency of 20.0 mA and a stimulus duration of 0.1 ms; peaks N1, P2, N2 using visual EPs, with a stimulus in the form of a flash of light, stimulus duration 10-20 ms; and peaks I, III, V using acoustic EPs with a stimulus of ±100 dB SPL, stimulus duration of 0.1 ms; if there are deviations in the obtained EP indicators from the normative indicators towards an increase or decrease in at least one of the specified types of EP, septic encephalopathy is detected.