Лечение ишемии мозга

Нужна информация о стандартах лечения Ишемии мозга в ранние сроки и в восстановительный период (использование актовегина, пирацетама, других препаратов) Имеется ли у кого опыт использования динамической доплерографии сосудов мозга при этом? Какие результаты и есть ли они? Работает ли кто в ранние сроки с неотоном и инстеноном?

[Ilya Safonov]

Стандартом лечения ишемии мозга в ранние сроки является дексаметазон. Что касается перечисленных Вами препаратов, то они играют вспомогательную роль. А что делаете Вы?

[PIV]

Илья Владимирович! Очень приятно вновь увидеть Вас в дискуссионном клубе. Дексаметазон - стандарт лечения ишемии до каких суток? Что Вы предлагаете на втором этапе.
Улучшение акушерской помощи? Ирина

Показана эффективность инстенона у новорожденных детей, на базе НМУ каф. детских инфекций (г.Киев). voronov@i.com.ua

ответ IgorF
имеем достаточно большой опыт около 200 динамических наболюдений доплерографии СМА, АСМ, АБ, венозного кровотока, параллельно с ЭХО сердца, реографией, экстракраниальной доплерографией у детей от 0-14 лет в основном при инфекционных поражениях ЦНС.

Доктору Воронову.
Наверняка при назначении того-же Инстенона Вы пользуетесь данными вышеперечисленных методов обследования. У нас кроме УЗИ г/м ничего нет, а кровоизлияния в ранние сроки им практически не визуализируются, Инстенон не применяем в первые 7 дней, и в принципе разницы в группах не видим. Случайно не наблюдали повторные ВЧК на Инстеноне?

Илье Владимировичу Сафонову.
Что касаемо дексазона - применяем всем тяжелым максимум 4-5 суток и то редко. Сейчас основной бич - инфекция. В принципе на ВУИ выходит до 70% детей, как бы не старались - поэтому неохота дополнительно бить по иммунитету, хоть и Пентаглобином периодами богаты.

Да, существует угроза повышение объемного кровотока на фоне применения инстенона и появление ВЖК и кровоизлияний в вещество мозга, противопоказанием для инстенона-судороги, повышение ВЧД. Изменение мозгового кровотока происходит в основном под действием этафиллина, по данным ЭХО-КГ проииходит снижение КСР и за счет этого увеличение ударнрого объема без повышение частоты и АД, при нарушении ауторегуляции возможно увеличение мозгового кровотока и появление осложнений.
Мы вышли из этой ситуации введением суточной дозы инстенона через дозатор в течении суток и резких колебаний центральной гемодинамики на наблюдали, а действие других компонетов инстенона достаточно хорошеее.
Все исследования под контролем и оценкой центральной и мозговой гемодинамики в течении суток не менее 1-2х раз.

Уважаемый доктор Сафонов,
упоминая дексаметазон как стандарт лечения ишемии мозга, какими источниками Вы пользовались?
Фомичев МВ.

[vlades]

Здавствуйте.
Тема достаточно интересная. И публикаций, часто достаточно противоречивых много.
По использованию попрепаратов Актовегин и Инстенон можно получить информацию на:
[Ссылки доступны только зарегистрированным пользователям ] и [Ссылки доступны только зарегистрированным пользователям ] Но профессор Шабалов отмечает в своей монографии "Лечение асфиксии новорожденных", что Солкосерил предпочтительнее.
Конечно, в данном плане интересны результаты инструментального контроля у Voronov Alex.

[vlg_asb]

Здравствуйте, все!

Буду крайне признателен за любые ссылки на доказательные исследования (Evidence-based ) по поводу хотя бы одного препарата, который бы улучшал мозговой кровоток. Боюсь, что их нет.

С уважением VLG_ASB.

[Dr.Vad]

Уважаемые коллеги!

Анализируя зарубежные публикации, обнаружил интересные наблюдения: дексаметазон не является больше стандартом в лечении ишемических/геморрагических инсультов:

Br Med J. 1978 Oct 7;2(6143):994-6.
Dexamethasone in acute stroke.

Mulley G, Wilcox RG, Mitchell JR.

Over 13 months 118 patients admitted to hospital with acute stroke were allocated at random to treatment with either dexamethasone or placebo. At one year there was no significant difference in the numbers of survivors or in the quality of life between the two groups. The results suggest that there is no indication for the routine administration of dexamethasone to a heterogeneous group of patients with stroke.



Br Med J (Clin Res Ed). 1986 Jan 4;292(6512):21-3.
High dose steroid treatment in cerebral infarction.
Norris JW, Hachinski VC.
Steroid treatment is widely used in acute cerebral infarction yet its value is controversial. High dose dexamethasone (480 mg over 12 days) was given in a double blind, randomised controlled trial to 113 consecutive eligible patients with acute cerebral infarction admitted to an acute stroke unit. Those with stroke for more than 48 hours, known embolic sources, diabetes, and infection were excluded. Death and quality of survival were recorded over 21 days. The active drug group (54 patients) matched the placebo group (59 patients) for age, initial stroke score, delay in beginning treatment, and other relevant variables. The two groups did not differ significantly in death rate or quality of survivorship. The small difference in mortality between the two groups may have represented a marginal therapeutic effect, which might reach significance in a larger sample. The widespread use of steroids in response to such a marginal therapeutic gain would expose large numbers of patients with stroke to more serious hazards of steroid treatment and convert patients who would otherwise have died into neurovegetative survivors. High dose steroid treatment was ineffective in ischaemic stroke, and the data suggest that further evaluation by a larger multicentre trial is not justified.

J Assoc Physicians India. 1989 May;37(5):315-7.
Role of dexamethasone in the outcome from acute stroke.
Kumar N, Jain S, Maheshwari MC.
Forty patients of acute stroke of less than 48 hours duration above the age of 40 years were studied. All patients were evaluated as per the evaluation scoring system at the time of admission within 24 hours and 7 days after admission to hospital. 25 patients were given dexamethasone and 15 patients who were not given dexamethasone were matched for age, sex, underlying diseases and clinical condition as per the evaluation scoring. The mean evaluation score in study group showed significant improvement at 7 days (p less than 0.05) as compared to control group. There was no significant difference in mortality between the study and control group, being 36% and 33% respectively. Functional status also remained identical in the two groups at the time of discharge. There was also no significant difference in the outcome of patients of intracerebral haemorrhage vs. cerebral infarction whether treated with dexamethasone or not.

West Afr J Med. 2001 Jan-Mar;20(1):1-6.
Effectiveness of high dose dexamethasone in the treatment of acute stroke.

Ogun SA, Odusote KA.

Department of Medicine, Ogun State University Teaching Hospital, Sagamu, Ogun State, Nigeria.

A prospective double-blind placebo-controlled, randomised clinical trial was carried out to determine the effectiveness of short-course of high dose dexamethasone therapy on mortality and neurological recovery in stroke patients. During a sixteen month period of study, 230 patients with clinical diagnosis of stroke were seen. Of these, 40 were eligible for the study (27 were presumed to have had haemorrhagic stroke; and 13 were presumed to have had cerebral infarction). The commonest cause of exclusion was presentation after 24 hours of the ictus. Patients were sequentially paired and randomised into high dose dexamethasone and placebo groups in a double-blind fashion. There were twenty patients in either group. Of the 27 patients with haemorrhagic stroke, 15 were in the dexamethasone group and 12 in the placebo group. Of the 13 patients with cerebral infarction, 5 were in the dexamethasone group and 8 in the placebo group. Each patient received 100 mg of dexamethasone stat, and 16 mg every 6 hours for a period of 48 hours or equivalent volumes of placebo. Assessment of each patient was done using a neurological score. Sequential analysis by Armitage was employed, using survival at 1 month as the primary criterion of effectiveness. Survivors were followed-up for 6 months. At the end of one month, 16 patients (80%) had died in the dexamethasone group and 17 (85%) in the placebo group. The average day of death was six days in the dexamethasone group and 15 days in the placebo group, but this was not statistically significant. Of the seven survivors at one month, four were in the dexamethasone group and 3 in the placebo group. Five of them had cerebral infarction and two had haemorrhagic stroke. The two in the haemorrhagic subgroup who survived the first month died at the 2nd and 4th month respectively. At the end of six months, only the five patients with cerebral infarction were alive. Of these, 2 in the dexamethasone group were back at work while the third was chair-bound. The 2 survivors in the placebo group were chair and bed bound respectively. In conclusion, this study failed to demonstrate any benefit of a short-course of high dose steroid in improving the mortality of stroke patients and its use should be discouraged.

Похоже, это стало понятно и индийцам и африканцам.

[Dr.Vad]

Дексаметазон может увеличивать церебральный кровоток у недоношенных, как было показано одной группой исследователей:

Eur J Pediatr. 1997 Jan;156(1):41-6.
Effect of dexamethasone therapy on cerebral and ocular blood flow velocity in premature infants studied by colour Doppler flow imaging.

Cabanas F, Pellicer A, Garcia-Alix A, Quero J, Stiris TA.

Department of Paediatrics, La Paz Children's Hospital, Madrid, Spain.

Although dexamethasone (DEX) is used widely in neonates with chronic, and even recently with acute respiratory disease, its potential side-effects on human cerebral and ocular haemodynamics remain unknown. The effects of DEX on cerebral and ocular blood flow velocities were assessed in preterm infants with lung disease and mechanical ventilation. Ten ventilated preterm infants received DEX (0.25 mg/kg/12 h) for ongoing chronic lung disease or extubation failure. Colour Doppler flow imaging studies of the internal carotid, anterior cerebral and ophthalmic arteries were made before and 10, 30, 60, 120 and 240 min after the 1st, 3rd, and 5th doses of DEX. Peak systolic, temporal mean, and end-diastolic flow velocities and the resistance index (RI) of Pourcelot were determined. The brain was examined by ultrasonography before and at the end of each Doppler study. All patients were continuously monitored for transcutaneous blood gases and blood pressure. All flow velocities and the RI of the internal carotid, anterior cerebral and ophthalmic arteries showed a similar trend throughout the study. The means of the values averaged for the 240 min of cerebral and ocular blood flow velocity with each dose were progressively higher and the values of the RI progressively lower up to the 5th dose. The most significant changes occurred in end-diastolic flow velocity and consisted of a percentage increase between the 1st and 5th dose of 72% in the internal carotid artery, 102% in the anterior cerebral artery and 84% in the ophthalmic artery. Changes in arterial blood pressure followed a pattern similar to that of changes in blood flow velocity. CONCLUSIONS: Dexamethasone increments cerebral and ocular blood flow velocity. We speculate that this finding may be relevant to the development of brain and retinal injury.

Arch Dis Child Fetal Neonatal Ed. 1998 Sep;79(2):F123-8.
Cerebral haemodynamics in preterm infants after exposure to dexamethasone.

Pellicer A, Gaya F, Stiris TA, Quero J, Cabanas F.

Division of Neonatology, La Paz Children's Hospital, Madrid, Spain.

AIM: To determine changes in brain haemodynamics produced by dexamethasone; to evaluate the pathophysiological conditions involved in the effect of dexamethasone. METHODS: A prospective study was made of 12 ventilated preterm infants who received dexamethasone (0.25 mg/kg/12 hours) for ongoing chronic lung disease or extubation failure. Cerebral blood flow (CBF), absolute cerebral blood volume (CBV), and cerebral blood volume changes (delta CBV) were estimated by near infrared spectroscopy, before and 10, 30, 60, 120, 180 and 240 minutes after the first, third, and fifth doses of dexamethasone. All patients were monitored continuously using pulse oximetry, transcutaneous blood gases, and blood pressure. RESULTS: There were significant short term changes in delta CBV on each day of the study; delta CBV increased significantly at 240 minutes compared with values before the first dose, and from 120 minutes onward during the third and fifth doses. However, mean CBV values averaged over 240 minutes after the first, third, and fifth doses did not vary. Mean CBF values averaged over 240 minutes increased progressively up to the fifth dose (significant differences between the first and fifth dose). The short term changes in CBF consisted of a significant increase 60 minutes after dexamethasone administration compared with the before and 10 minute values in every study. Blood pressure was significantly higher in the third and fifth doses than in the first dose. Blood pressure showed no short term changes. There was no correlation between CBF and blood pressure changes. TcPCO2 (transcutaneous PCO2) decreased significantly throughout the study period, with the average mean value in the fifth dose significantly lower than in the first dose. Nevertheless, no short term changes in TcPCO2 were observed. CONCLUSIONS: Postnatal systemic dexamethasone administration produced significant changes in cerebral haemodynamics that seemed to be related to both a direct effect on regional vessel walls and the cumulative effect of dexamethasone.

другие исследователи у других детей этого не обнаружили, но нашли незначительное снижение скорости кровотока:
Eur J Pediatr. 1994 May;153(5):363-6.
The effect of dexamethasone on time averaged mean velocity in the middle cerebral artery in very low birth weight infants.

Ohlsson A, Bottu J, Govan J, Ryan ML, Myhr T, Fong K.

Department of Newborn and Developmental Paediatrics, Women's College Hospital, Toronto, Ontario, Canada.

The effect of repeated doses of dexamethasone (0.25 mg/kg/dose every 12 h) on time averaged mean velocity in the middle cerebral artery was assessed in ten ventilated very low birth weight infants requiring treatment with dexamethasone for bronchopulmonary dysplasia or airway obstruction. The infants were studied by colour/duplex Doppler technique prior to the administration of the first and the third dose of dexamethasone, and 10, 30, and 120 min after these doses. Dexamethasone treatment was associated with an improvement in infant lung condition, an increase in mean arterial blood pressure and a decrease in heart rate. The time averaged mean velocity was statistically significantly reduced at 120 min after the first dose. This was not associated with a decrease in PCO2. The observed reduction of 18% from baseline in the time averaged mean velocity is unlikely to be of clinical importance.

[Dr.Vad]

Применение актовегинов, инстенонов, солкосерилов и пр. "ноометаболотропов" не обнаружено у новорожденных, но среди обнаруживаемых публикаций на основании других слоев населения преобладают отечественные.
Пирацетам также нечасто пользуют среди новорожденных:
Pediatr Neurol. 1998 Jan;18(1):41-5.
Clinical efficacy of piracetam in treatment of breath-holding spells.
Donma MM.
Ministry of Health, Bakirkoy State Hospital, Clinics of Paediatrics, Istanbul, Turkey.
To evaluate the efficacy of piracetam therapy, 76 children with breath-holding spells admitted to the Outpatient Clinic of Dicle University Medical Faculty Paediatrics Department and Bakirkoy State Hospital, Paediatrics Department between 1988 and 1990 and 1991 and 1996, respectively, were included in this placebo-controlled trial. Diagnosis of breath-holding spells was made for all cases by medical history, pediatric physical examination, electroencephalogram, and laboratory findings. Placebo or piracetam as suspension was administered to patients on a randomized basis; piracetam was administered to children in suspension 40 mg/kg/day in 2 divided doses for a period of 2 months. Of the 76 children enrolled, 39 received piracetam and 37 received placebo. Overall, control of breath-holding spells was observed in 92.3% of the patients in the group taking piracetam as compared with 29.7% in the group taking placebo (P < .05). No differences between the 2 groups in adverse events or side effects were observed. Complete blood count, biochemical profile, and urine analysis taken before and after treatment revealed no change from beginning to end and no difference between the 2 groups. It is suggested that piracetam is a safe and effective drug, with an incidence of side effects no different from that of placebo, for the treatment of breath-holding spells.

Neuropediatrics. 2002 Feb;33(1):41-2.
Breath holding spells in a 3-day-old neonate: an unusual early presentation in a family with a history of breath holding spells.

Breukels MA, Plotz FB, van Nieuwenhuizen O, van Diemen-Steenvoorde JA.

Department of Pediatrics, St. Antonius Hospital, Nieuwegein, The Netherlands.

Breath holding spells are common in childhood. They peak about 2 years of age and abate by 5 years of age; they are rare before 6 months of age. We report a case of cyanotic breath holding spells starting at the age of 3 days. There was a family history of breath holding spells including a three-year-old brother, patient's father, his sister, and the paternal great grandfather. Pharmacological intervention with iron replacement therapy and piracetam was not successful. We want to draw attention to the fact that breath holding spells should be included in the differential diagnosis of neonatal cyanotic spells. The course of these neonatal breath holding spells is thought to be "benign", but nevertheless, severe breath holding spells can pose problems for parents and clinicians.

Что же касается пирацетама в лечении инсультов, то похоже что кое-кому он может быть полезным:

Stroke. 1997 Dec;28(12):2347-52.
Treatment of acute ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study (PASS) Group.

De Deyn PP, Reuck JD, Deberdt W, Vlietinck R, Orgogozo JM.

Department of Neurology, Middelheim Hospital, Antwerp, Belgium.

BACKGROUND AND PURPOSE: Piracetam, a nootropic agent with neuroprotective properties, has been reported in pilot studies to increase compromised regional cerebral blood flow in patients with acute stroke and, given soon after onset, to improve clinical outcome. We performed a multicenter, randomized, double-blind trial to test whether piracetam conferred benefit when given within 12 hours of the onset of acute ischemic stroke to a large group of patients. METHODS: Patients received placebo or 12 g piracetam as an initial intravenous bolus, 12 g daily for 4 weeks and 4.8 g daily for 8 weeks. The primary end point was neurologic outcome after 4 weeks as assessed by the Orgogozo scale. Functional status at 12 weeks as measured by the Barthel Index was the major secondary outcome. CT scan was performed within 24 hours of the onset of stroke but not necessarily before treatment. Analyses based on the intention to treat were performed in all randomized patients (n = 927) and in an "early treatment" population specified in the protocol as treatment within 6 hours of the onset of stroke but subsequently redefined as less than 7 hours after onset (n = 452). RESULTS: In the total population, outcome was similar with both treatments (the mean Orgogozo scale after 4 weeks: piracetam 57.7, placebo 57.6; the mean Barthel Index after 12 weeks: piracetam 55.8, placebo 53.1). Mortality at 12 weeks was 23.9% (111/464) in the piracetam group and 19.2% (89/463) in the placebo group (relative risk 1.24, 95% confidence interval, 0.97 to 1.59; P = .15). Deaths were fewer in the piracetam group in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke. Post hoc analyses in the early treatment subgroup showed differences favoring piracetam relative to placebo in mean Orgogozo scale scores after 4 weeks (piracetam 60.4, placebo 54.9; P = .07) and Barthel Index scores at 12 weeks (piracetam 58.6, placebo 49.4; P = .02). Additional analyses within this subgroup, confined to 360 patients with moderate and severe stroke (initial Orgogozo scale score < 55), showed significant improvement on piracetam in both outcomes (P < .02). CONCLUSIONS: Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke. Post hoc analyses suggest that piracetam may confer benefit when given within 7 hours of onset, particularly in patients with stroke of moderate and severe degree. A randomized, placebo-controlled, multicenter study, the Piracetam Acute Stroke Study II (PASS II) will soon begin.

Окончательных выводов дождемся из PASS II.

[yananshs]

[Ссылки доступны только зарегистрированным пользователям ]


Корректность лечения гипоксических поражений головного мозга новорожденных
Пальчик А.Б., Шабалов Н.П.
Гипоксически-ишемическая энцефалопатия новорожденных: руководство для врачей. СПб: "Питер", 2000

В соответствующем разделе изложены основные принципы лечения гипоксических поражений головного мозга новорожденных. Между тем, в неонатологической и неврологической практике широко используются препараты различных групп, чей эффект адекватно не изучен у новорожденных и чья структура вызывает существенные возражения против применения их у новорожденных.

Так называемые вазоактивные препараты. К ним относят препараты различных групп (в частности, блокаторы медленных Са2+-каналов - циннаризин, производные винкаминовой кислоты - кавинтон и т. д.). Возражение против назначения вазоактивных препаратов заключается в следующем:
препараты не проверены "двойным слепым" методом;
не известна интенсивность мозгового кровотока у данного ребенка;
если интенсивность мозгового кровотока известна, то не ясно, является ли настоящая церебральная перфузия адаптационной или патологической в связи с существенными колебаниями уровня церебральной перфузии у новорожденного после рождения;
каким целям служит назначение вазоактивного препарата: ликвидации гиперперфузии или ликвидации гипоперфузии и нужно ли этого достигать на данные сутки жизни, у данного ребенка; что означает "улучшить" мозговой кровоток?
Препараты, содержащие гидролизаты аминокислот, нейропептидов и т.д.
К таким препаратам можно отнести церебролизин, актовегин, солкосерил, кортрексин. Возражение против назначения этих препаратов заключается в том, что:
препараты не проверены "двойным слепым" методом, а в некоторых случаях вообще не подлежали никакому серьезному фармакологическому контролю;
содержат в себе неконтролируемые концентрации противоположных по механизму действия биологически активных ингредиентов (например, в солкосериле содержатся глютамат и аспартат - возбуждающие аминокислоты и глицин - тормозная аминокислота, пропорции их содержания не известны; не ясна потребность ребенка в этих аминокислотах на различных стадиях НГИЭ, в одной из которых преобладает возбуждение ребенка, в других - угнетение);
фармакодинамика ряда препаратов оказывает нежелательный эффект при гипоксии (в частности, "антигипоксант" солкосерил повышает потребление клетками кислорода, что является одним из нейрон-повреждающих факторов в развитии НГИЭ);
являются гидролизатами, как правило, крови крупного рогатого скота, и таким образом обладают аллергогенным действием; некоторые препараты имеют отчетливые побочные эффекты (например, церебролизин часто провоцирует возбуждение и судороги у детей).
ГАМК-ергические препараты (пирацетам, аминалон, фенибут, пантогам, пикамилон).
Возражение к использованию этих препаратов основано только на отсутствии контролируемых исследований с доказательством эффективности их действия.
Подобные замечания относятся также к ряду фитотерапевтических и гомеопатических средств.