Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial)

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• 作者：Glenn M. Eastwood^a ; ^{glenn.eastwood@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; ^{gmeastwood@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Antoine G. Schneider^b ; ^{Antoine.Schneider@chuv.ch" class="auth_mail" title="E-mail the corresponding author} ; Satoshi Suzuki^c ; ^{Suzuki-s@mtc.biglobe.ne.jp" class="auth_mail" title="E-mail the corresponding author} ; Leah Peck^a ; ^{leah.peck@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Helen Young^a ; ^{helen.young@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Aiko Tanaka^a ; ^{aiko.tanaka@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Johan Må ; rtensson^a ; ^{johan.martensson@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Stephen Warrillow^a ; ^{stephen.warrillow@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Shay McGuinness^d ; ^{ShayMc@adhb.govt.nz" class="auth_mail" title="E-mail the corresponding author} ; Rachael Parke^d ; ^{RParke@adhb.govt.nz" class="auth_mail" title="E-mail the corresponding author} ; Eileen Gilder^d ; ^{EGilder@adhb.govt.nz" class="auth_mail" title="E-mail the corresponding author} ; Lianne Mccarthy^d ; ^{LianneM@adhb.govt.nz" class="auth_mail" title="E-mail the corresponding author} ; Pauline Galt^e ; ^{Pauline.Galt@monashhealth.org" class="auth_mail" title="E-mail the corresponding author} ; Gopal Taori^e ; ^{Gopal.Taoiri@monashhealth.org" class="auth_mail" title="E-mail the corresponding author} ; Suzanne Eliott^e ; ^{Suzanne.Eliott@monashhealth.org" class="auth_mail" title="E-mail the corresponding author} ; Tammy Lamac^f ; ^{tammy.lamac@easternhealth.org.au" class="auth_mail" title="E-mail the corresponding author} ; Michael Bailey^g ; ^{michael.bailey@monash.edu" class="auth_mail" title="E-mail the corresponding author} ; Nerina Harley^h ; ^{Nerina.harley@rmh.org.au" class="auth_mail" title="E-mail the corresponding author} ; Deborah Barge^h ; ^{Deborah.barge@mh.org.au" class="auth_mail" title="E-mail the corresponding author} ; Carol L. Hodgsonⁱ ; ^{carol.hodgson@monash.edu" class="auth_mail" title="E-mail the corresponding author} ; Maria Cristina Morganti-Kossmann^j ; ^k ; ^{Cristina.morganti-kossmann@monash.edu" class="auth_mail" title="E-mail the corresponding author} ; Alice Pé ; bay^l ; ^m ; ^{bay@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author} ; Alison Conquest^l ; ^m ; ^{alison.conquest@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author} ; John S. Archerⁿ ; ^{jarcher@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author} ; Stephen Bernard^j ; ^{S.Bernard@alfred.org.au" class="auth_mail" title="E-mail the corresponding author} ; Dion Stub^o ; ^{d.stub@alfred.org.au" class="auth_mail" title="E-mail the corresponding author} ; Graeme K. Hart^a ; ^{graeme.hart@austin.org.au" class="auth_mail" title="E-mail the corresponding author} ; Rinaldo Bellomo^a ; ^{rinaldo.bellomo@austin.org.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Carbon dioxide ; Cardiac arrest ; Hypercapnia ; Mechanical ventilation ; Mortality ; Intensive care
• 刊名：Resuscitation
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：104
• 期：Complete
• 页码：83-90
• 全文大小：470 K

文摘

In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested.

Methods

In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24 h of targeted normocapnia (TN) (PaCO₂ 35–45 mmHg) or TTMH (PaCO₂ 50–55 mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72 h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients.

Results

We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment.

NSE concentrations increased in the TTMH group (p = 0.02) and TN group (p = 0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p < 0.001) but not in the TN group (p = 0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p = 0.31).

Conclusions

In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.