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

Glenn M. Eastwood, Antoine G. Schneider, Satoshi Suzuki, Leah Peck, Helen Young, Aiko Tanaka, Johan Mårtensson, Stephen Warrillow, Shay McGuinness, Rachael Parke, Eileen Gilder, Lianne Mccarthy, Pauline Galt, Gopal Taori, Suzanne Eliott, Tammy Lamac, Michael Bailey, Nerina Harley, Deborah Barge, Carol L. HodgsonMaria Cristina Morganti-Kossmann, Alice Pébay, Alison Conquest, John S. Archer, Stephen Bernard, Dion Stub, Graeme K. Hart, Rinaldo Bellomo

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background: 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.

Original languageEnglish
Pages (from-to)83-90
Number of pages8
JournalResuscitation
Volume104
DOIs
Publication statusPublished - Jul 1 2016

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Hypercapnia
Heart Arrest
Randomized Controlled Trials
Phosphopyruvate Hydratase
Therapeutics
Safety
Critical Care
Hospital Mortality
Observational Studies
Biomarkers

Keywords

  • Carbon dioxide
  • Cardiac arrest
  • Hypercapnia
  • Intensive care
  • Mechanical ventilation
  • Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Emergency
  • Emergency Medicine

Cite this

Targeted therapeutic mild hypercapnia after cardiac arrest : A phase II multi-centre randomised controlled trial (the CCC trial). / Eastwood, Glenn M.; Schneider, Antoine G.; Suzuki, Satoshi; Peck, Leah; Young, Helen; Tanaka, Aiko; Mårtensson, Johan; Warrillow, Stephen; McGuinness, Shay; Parke, Rachael; Gilder, Eileen; Mccarthy, Lianne; Galt, Pauline; Taori, Gopal; Eliott, Suzanne; Lamac, Tammy; Bailey, Michael; Harley, Nerina; Barge, Deborah; Hodgson, Carol L.; Morganti-Kossmann, Maria Cristina; Pébay, Alice; Conquest, Alison; Archer, John S.; Bernard, Stephen; Stub, Dion; Hart, Graeme K.; Bellomo, Rinaldo.

In: Resuscitation, Vol. 104, 01.07.2016, p. 83-90.

Research output: Contribution to journalArticle

Eastwood, GM, Schneider, AG, Suzuki, S, Peck, L, Young, H, Tanaka, A, Mårtensson, J, Warrillow, S, McGuinness, S, Parke, R, Gilder, E, Mccarthy, L, Galt, P, Taori, G, Eliott, S, Lamac, T, Bailey, M, Harley, N, Barge, D, Hodgson, CL, Morganti-Kossmann, MC, Pébay, A, Conquest, A, Archer, JS, Bernard, S, Stub, D, Hart, GK & Bellomo, R 2016, 'Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial)', Resuscitation, vol. 104, pp. 83-90. https://doi.org/10.1016/j.resuscitation.2016.03.023
Eastwood, Glenn M. ; Schneider, Antoine G. ; Suzuki, Satoshi ; Peck, Leah ; Young, Helen ; Tanaka, Aiko ; Mårtensson, Johan ; Warrillow, Stephen ; McGuinness, Shay ; Parke, Rachael ; Gilder, Eileen ; Mccarthy, Lianne ; Galt, Pauline ; Taori, Gopal ; Eliott, Suzanne ; Lamac, Tammy ; Bailey, Michael ; Harley, Nerina ; Barge, Deborah ; Hodgson, Carol L. ; Morganti-Kossmann, Maria Cristina ; Pébay, Alice ; Conquest, Alison ; Archer, John S. ; Bernard, Stephen ; Stub, Dion ; Hart, Graeme K. ; Bellomo, Rinaldo. / Targeted therapeutic mild hypercapnia after cardiac arrest : A phase II multi-centre randomised controlled trial (the CCC trial). In: Resuscitation. 2016 ; Vol. 104. pp. 83-90.
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T2 - A phase II multi-centre randomised controlled trial (the CCC trial)

AU - Eastwood, Glenn M.

AU - Schneider, Antoine G.

AU - Suzuki, Satoshi

AU - Peck, Leah

AU - Young, Helen

AU - Tanaka, Aiko

AU - Mårtensson, Johan

AU - Warrillow, Stephen

AU - McGuinness, Shay

AU - Parke, Rachael

AU - Gilder, Eileen

AU - Mccarthy, Lianne

AU - Galt, Pauline

AU - Taori, Gopal

AU - Eliott, Suzanne

AU - Lamac, Tammy

AU - Bailey, Michael

AU - Harley, Nerina

AU - Barge, Deborah

AU - Hodgson, Carol L.

AU - Morganti-Kossmann, Maria Cristina

AU - Pébay, Alice

AU - Conquest, Alison

AU - Archer, John S.

AU - Bernard, Stephen

AU - Stub, Dion

AU - Hart, Graeme K.

AU - Bellomo, Rinaldo

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background: 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.

AB - Background: 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.

KW - Carbon dioxide

KW - Cardiac arrest

KW - Hypercapnia

KW - Intensive care

KW - Mechanical ventilation

KW - Mortality

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