CORTICUS

[thorn]

Получил с очередной рассылкой [Ссылки доступны только зарегистрированным пользователям ] (вроде нужна регистрация)

...Dr. Charles Sprung, of Hadassah Hospital, presented the actual randomized clinical trial (RCT) results from CORTICUS. He humorously started by suggesting that utilization of corticosteroids in the ICU was more a reflection of belief systems than of rigorous clinical trials. It was this long-term controversy that prompted the need for CORTICUS. Again, reminding the audience of recent randomized studies of this question, Dr. Sprung outlined the findings of Annane and colleagues.[3] In persons with refractory shock begun on glucocorticoids and mineralocorticoids within 8 hours, there was a mortality benefit in cortrosyn stimulation-challenged "nonresponders." To confirm and to build on these findings, CORTICUS represented a multicenter, international, double-blind RCT. The primary end point was 28-day all-cause mortality in "nonresponders" (defined as a change of ≤ 9 mcg/dL in cortisol after a 250-mcg cortrosyn stimulation test). Secondary end points dealt with mortality in the entire population, organ failure resolution, and safety. The study was conducted from March 2002 through November 2005 at 52 sites in Europe and the Middle East. The study was designed to enroll 800 patients so that it would have sufficient power to detect a 10% difference in mortality. However, because of difficulty with recruitment, the trial was halted after 500 persons were enrolled. Inclusion criteria included: evidence of infection along with 2 or more SIRS criteria, shock within the prior 72 hours (defined as systolic blood pressure < 90 mm Hg or the need for vasopressors), and signs of hypoperfusion. Patients chronically on corticosteroids, those with advanced directives, immunosuppressed persons, and moribund subjects were excluded.
Initially, participants were given 50 mg of hydrocortisone every 6 hours for 5 days with a tapering dose over the next 6 days. Fludricortisone was not administered.
There were no differences in these baseline characteristics or the severity of illness between the 2 cohorts. For no outcome end point did there appear to be a difference with use of corticosteroids. All-cause mortality was similar between the 2 arms (34% corticosteroids vs 31% placebo). Mortality rates also did not vary based on responder status. However, nonresponders tended to have higher mortality overall. Overall, rates of shock reversal appeared better in those given corticosteroids. This difference was not statistically significant; however, in the subgroup of responders, time to shock reversal appeared faster.
With a note of caution, Dr. Sprung reviewed the safety data. Rates of superinfection were higher in those given corticosteroids (34% vs 27%, P = .099). The frequency of hospital-acquired new sepsis was also higher in those randomized to steroids. Hyperglycemia, not surprising, was also more common on study day 1 in persons treated with corticosteroids.
What explains these findings and why do they differ from earlier trials and meta-analyses?[4] First, Dr. Sprung suggested that compared with the report by Annane and colleagues,[3] those in this study were not as severely ill. The total mortality rate in the Annane trial approached 60% vs 34% in CORTICUS. Similarly, the allowable duration of shock prior to enrollment was shorter in the Annane protocol. Relatedly, perhaps there was some difference due to the withholding of fludricortisone or due to the fact that CORTICUS encouraged physicians to follow current sepsis guidelines.
Whatever the reason, the findings of CORTICUS give pause to those who have advocated more frequent use of corticosteroids in septic shock.[4] Even though it was underpowered, there seems to be no hint of a signal favoring broader use of corticosteroids. Additionally, there may be an indication of harm given the data about superinfection. Further analyses are planned and hopefully these will prove enlightening. Clinicians, nonetheless, must choose if and how to utilize corticosteroids. Hence, restricting their employment to persons who resemble those studied by Annane and colleagues might be the most prudent course as there are clinical trial findings to support this. Broad, routine administration of corticosteroids in severe sepsis and shock seems unwarranted at present.

Сообщение от thorn

Broad, routine administration of corticosteroids in severe sepsis and shock seems unwarranted at present.

Минус еще одна терапевтическая возможность при септическом шоке. Жаль, но вполне убедительно

::.. выкидываем гидрокортизон, покупаем селен ..::

[Dr. Giggles]

Уважаемые коллеги! Попытаюсь задать вопрос от обратного - Где все еще оправдано применение глюкокортикоидов (применительно к интенсивной терапии). При каких состояниях требуется их назначение?

В нашей местности в обязательном порядке назначают
1. при синдроме системного воспалительного ответа (SIRS) - мотивируя это профилактикой развития септического шока. При шоке само собой
2. массивных кровотечениях в т.ч. акушерских - обосновывая назначения блокадой фибринолиза.
3. Менингококковый сепсис (чаще) - маленькие дети с синдромом Уотерхауса - Фридериксена - заместительная терапия острой надпочечниковой недостаточности. ГКС назначаются и без шока при менингите - "профилактика шока", "противоотечная цель" в т.ч. и при серозных менингитах.
4. Надпочечниковая недостаточность несвязанная с инфекцией - заместительная терапия.
5. Тяжелый вирусный гепатит - фульминантный гепатит - подавление воспаления, аутоиммунной агрессиии в отношении гепатоцитов.
6. Различные варианты назначения без обоснования вовсе...

Понимаю абсурдность и архаичность некоторых показаний, но все же хотелось бы услышать и Ваше мнение!

Best regards!

[thorn]

Сообщение от Dr. Giggles

1. при синдроме системного воспалительного ответа (SIRS) - мотивируя это профилактикой развития септического шока. При шоке само собой

Об этом как раз речь в этой ветке...

Сообщение от Dr. Giggles

2. массивных кровотечениях в т.ч. акушерских - обосновывая назначения блокадой фибринолиза.

Не знаю...

Сообщение от Dr. Giggles

3. Менингококковый сепсис (чаще) - маленькие дети с синдромом Уотерхауса - Фридериксена - заместительная терапия острой надпочечниковой недостаточности. ГКС назначаются и без шока при менингите - "профилактика шока", "противоотечная цель" в т.ч. и при серозных менингитах.

У взрослых при менингите - однозначно (перед или вместе с первым введением а/б по 10 мг декса 4 р/сут на 4 дня)... Как раз свежий кокрановский обзор в тему:

Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004405.

Corticosteroids for acute bacterial meningitis.

van de Beek D, de Gans J, McIntyre P, Prasad K.

BACKGROUND: In experimental studies, the clinical outcome of acute bacterial meningitis has been related to the severity of the inflammatory process in the subarachnoidal space. Treatment with corticosteroids can reduce this inflammatory response and thereby may improve outcome. We conducted a meta-analysis of randomised controlled trials (RCTs) of adjuvant corticosteroids in the treatment of acute bacterial meningitis. OBJECTIVES: We conducted a systematic review examining the efficacy and safety of adjuvant corticosteroid therapy in acute bacterial meningitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2006); MEDLINE (1966 to July 2006); EMBASE (1974 to June 2006); Current Contents (2001 to June 2006); and reference lists of all articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Eligible published and non-published RCTs on corticosteroids as adjuvant therapy in acute bacterial meningitis. Patients of any age and in any clinical condition, treated with antibacterial agents and randomised to corticosteroid therapy (or placebo) of any type, could be included. At least case fatality rate or hearing loss had to be recorded for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Adverse effects were collected from the trials. Additional analyses were performed for children and adults, causative organisms, and low-income and developed countries. MAIN RESULTS: Eighteen studies involving 2750 people were included. Overall, adjuvant corticosteroids were associated with lower case fatality (relative risk (RR) 0.83, 95% CI 0.71 to 0.99), lower rates of severe hearing loss (RR 0.65, 95% CI 0.47 to 0.91) and long-term neurological sequelae (RR 0.67, 95% CI 0.45 to 1.00). In children, corticosteroids reduced severe hearing loss (RR 0.61, 95% CI 0.44 to 0.86). In adults, corticosteroids gave significant protection against death (RR 0.57, 95% CI 0.40 to 0.81) and short-term neurological sequelae (RR 0.42, 95% CI 0.22 to 0.87). Subgroup analysis for causative organisms showed that corticosteroids reduced mortality in patients with meningitis due to Streptococcus pneumoniae (RR 0.59, 95% CI 0.45 to 0.77) and reduced severe hearing loss in children with meningitis due to Haemophilus influenzae (RR 0.37, 95% CI 0.20 to 0.68); subgroup analysis for patients with meningococcal showed a nonsignificant favourable trend in mortality (RR 0.71, 95% CI 0.31 to 1.62). Sub analyses for high-income and low-income countries of the effect of corticosteroids on mortality showed RRs of 0.83 (95% CI 0.52 to 1.05) and 0.87 (95% CI 0.72 to 1.05), respectively. Corticosteroids were protective against short-term neurological sequelae in patients with bacterial meningitis high-income countries (RR 0.56, 95% CI 0.3 to 0.84); in low-income countries this RR was 1.09 (95% CI 0.83 to 1.45). For children with bacterial meningitis admitted in high-income countries, corticosteroids showed a protective effect of on severe hearing loss (RR 0.61, 95% CI 0.41 to 0.90) and favourable point estimates for severe hearing loss associated with non-Haemophilus influenzae meningitis (RR 0.51, 95% CI 0.23 to 1.13) and short-term neurological sequelae (RR 0.72, 95% CI 0.39 to 1.33). For children in low-income countries, the use of corticosteroids was neither associated with benefit nor with harmful effects. Overall, adverse events were not increased significantly with the use of corticosteroids. AUTHORS' CONCLUSIONS: Overall, corticosteroids significantly reduced rates of mortality, severe hearing loss and neurological sequelae. In adults with community-acquired bacterial meningitis, corticosteroid therapy should be administered in conjunction with the first antibiotic dose. In children, data support the use of adjunctive corticosteroids in children in high-income countries. We found no beneficial effect of corticosteroids for children in low-income countries.

Сообщение от Dr. Giggles

4. Надпочечниковая недостаточность несвязанная с инфекцией - заместительная терапия.

Это вроде понятно...

Сообщение от Dr. Giggles

5. Тяжелый вирусный гепатит - фульминантный гепатит - подавление воспаления, аутоиммунной агрессиии в отношении гепатоцитов.

Неэффективны, могут быть вредны (кроме аутоиммунного и вроде как алкогольного)

Сообщение от Dr. Giggles

6. Различные варианты назначения

Пневмоцистная пневмония, туберкулезный менингит и т.д. Неплохой обзор [Ссылки доступны только зарегистрированным пользователям ] Там можно зарегиться на free trial и брать полный текст в течение недели... Если сложности какие - вышлю на мыло.

[DmitryTro]

пункт 1 - только при грам- (в основном менингококковом) шоке, как правило однократно - подавление синтеза цитокинов (под большим вопросом).
пункт 3 с некоторыми изменениями: при менингококковом менингите у детей - кортикостероиды (дексазон) - снижение летальности, улучшение исходов (кроме "профилактика шока")
пункт 4 - так же
пункт 5 - так же

Особенно понравилось при SIRS - новомодное творчество, главное чтобы начальство такое не увидело.

[Dr. Giggles]

Сообщение от DmitryTro

Особенно понравилось при SIRS - новомодное творчество, главное чтобы начальство такое не увидело.

Спасибо за коментарии. Мне тоже "нравится", но стандарт апруван начальством, также как и периоперационная старвация, клизмы и т.д.

[thorn]

Сообщение от DmitryTro

с некоторыми изменениями: при менингококковом менингите у детей - кортикостероиды (дексазон) - снижение летальности, улучшение исходов (кроме "профилактика шока")

Интересно, что именно при менингококковом менингите польза от кортикостероидов не очевидна. В анализе подгрупп в приведенном выше кокрановском обзоре это хорошо видно... Может все дело в дозах? Одно дело по 50 мг гидро 4 р/сут а другое по 10 мг декса 4 р/сут?

[Dr. Giggles]

Сообщение от thorn

Интересно, что именно при менингококковом менингите польза от кортикостероидов не очевидна. В анализе подгрупп в приведенном выше кокрановском обзоре это хорошо видно... Может все дело в дозах? Одно дело по 50 мг гидро 4 р/сут а другое по 10 мг декса 4 р/сут?

Прошу прощения! Вопрос: Почему же применение ГКС у детей из слаборазвитых (с низкими доходами) стран бесполезно, а высокоразвитых их назначать следует? Может выбор антибиотика, доз?

По поводу применения ГКС

Corticosteroids in adult
meningitis (see refs)
• Dexamethasone 0.15mg/kg qds for 4 days
started with or just before the first dose of
antibiotics, particularly where
pneumococcal meningitis is suspected
• Do not give unless you are confident you
are using the correct antimicrobials
• Stop the dexamethasone if a non-bacterial
cause is identified

Взято здесь: [Ссылки доступны только зарегистрированным пользователям ]
Полный алгоритм лечебно-диагностических мероприятий (management) при подозрении на бак менингит и менингококковый сепсис у взрослых

Новый мета-анализ от Annane с коллегами опубликован в недавнем номере JAMA. Даже не смотря на включение в анализ исследования CORTICUS, общие результаты показали, что использование продленного курса низких доз кортикостероидов снижало летальность у больных с тяжелым сепсисом и септическим шоком.

Context The benefit of corticosteroids in severe sepsis and septic shock remains controversial.

Objective We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration.

Data Sources We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors.

Study Selection Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included.

Data Extraction All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials’ authors whenever possible. Some unpublished data were obtained from the trials’ authors. The primary outcome for this review was 28-day mortality.

Results We identified 17 randomized trials (n=2138) and 3 quasi-randomized trials (n=246) that had acceptable methodological quality to pool in a meta-analysis. Twentyeight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P=.05; I2=53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P=.83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P=.02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P=.02; I2=4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, –7.04 to –1.94; P
.001; I2=0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P=.50; I2=0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P=.92; I2=8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P=.58; I2=30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P
.001; I2=0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P
.001; I2=0%).

Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.

Редакционный комментарий в журнале имеет характерное зназвание:
Living With Uncertainty in the Intensive Care Unit. Should Patients With Sepsis Be Treated With Steroids? - И, по большому счету не дает ответа на этот вопрос.

[dmblok]

Сообщение от zubarew

Новый мета-анализ от Annane с коллегами опубликован в недавнем номере JAMA. Даже не смотря на включение в анализ исследования CORTICUS, общие результаты показали, что использование продленного курса низких доз кортикостероидов снижало летальность у больных с тяжелым сепсисом и септическим шоком..

Djillali Annane; Eric Bellissant; Pierre-Edouard Bollaert; et al.
Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults: A Systematic Review
JAMA. 2009;301(22):2362-2375

[Ссылки доступны только зарегистрированным пользователям ]

Сообщение от zubarew

Редакционный комментарий в журнале имеет характерное зназвание:
Living With Uncertainty in the Intensive Care Unit. Should Patients With Sepsis Be Treated With Steroids? - И, по большому счету не дает ответа на этот вопрос.

Roman Jaeschke; Derek C. Angus
Living With Uncertainty in the Intensive Care Unit: Should Patients With Sepsis Be Treated With Steroids?
JAMA. 2009;301(22):2388-2390

[Ссылки доступны только зарегистрированным пользователям ]

Кому интересно, здесь вы можете прочитать в сокращенном изложении на русском обсуждаемый мета-анализ из журнала JAMA ( http://www.medmir.com/content/view/2580/64/ )

.. и редакционную статью к ней ( http://www.medmir.com/content/view/2581/64/ ).