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Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: an exploratory Target Temperature Management Trial substudy

Authors: Florian Ebner, Matt B. A. Harmon, Anders Aneman, Tobias Cronberg, Hans Friberg, Christian Hassager, Nicole Juffermans, Jesper Kjærgaard, Michael Kuiper, Niklas Mattsson, Paolo Pelosi, Susann Ullén, Johan Undén, Matt P. Wise, Niklas Nielsen

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients and its association to neurological outcome is undetermined.

Methods

This is an exploratory post-hoc substudy of the Target Temperature Management (TTM) trial, including resuscitated OHCA patients, investigating the association between serial measurements of arterial partial carbon dioxide pressure (PaCO2) and neurological outcome at 6 months, defined by the Cerebral Performance Category (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3–5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2 and absolute PaCO2 difference were analyzed. Additionally, the association between mild hypercapnia (6.0–7.30 kPa) and neurological outcome, its interaction with target temperature (33 °C and 36 °C), and the association between PaCO2 and peak serum-Tau were evaluated.

Results

Of the 939 patients in the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients were exposed to hypocapnia or hypercapnia. None of the analyses indicated a statistical significant association between PaCO2 and neurological outcome (P = 0.13–0.96). Mild hypercapnia was not associated with neurological outcome (P = 0.78) and there was no statistically significant interaction with target temperature (Pinteraction = 0.95). There was no association between PaCO2 and peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC).

Conclusions

Dyscarbia is common after ROSC. No statistically significant association between PaCO2 in the post-cardiac arrest phase and neurological outcome at 6 months after cardiac arrest was detected. There was no significant interaction between mild hypercapnia and temperature in relation to neurological outcome.
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Literature
1.
go back to reference Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation. 2010;81(11):1479–87.CrossRefPubMed Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation. 2010;81(11):1479–87.CrossRefPubMed
2.
go back to reference Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–e360.CrossRefPubMed Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–e360.CrossRefPubMed
3.
go back to reference Kudenchuk PJ, Sandroni C, Drinhaus HR, Bottiger BW, Cariou A, Sunde K, Dworschak M, Taccone FS, Deye N, Friberg H, et al. Breakthrough in cardiac arrest: reports from the 4th Paris International Conference. Ann Intensive Care. 2015;5(1):22.CrossRefPubMedPubMedCentral Kudenchuk PJ, Sandroni C, Drinhaus HR, Bottiger BW, Cariou A, Sunde K, Dworschak M, Taccone FS, Deye N, Friberg H, et al. Breakthrough in cardiac arrest: reports from the 4th Paris International Conference. Ann Intensive Care. 2015;5(1):22.CrossRefPubMedPubMedCentral
4.
go back to reference Kragholm K, Wissenberg M, Mortensen RN, Hansen SM, Malta Hansen C, Thorsteinsson K, Rajan S, Lippert F, Folke F, Gislason G, et al. Bystander efforts and 1-year outcomes in out-of-hospital cardiac arrest. N Engl J Med. 2017;376(18):1737–47.CrossRefPubMed Kragholm K, Wissenberg M, Mortensen RN, Hansen SM, Malta Hansen C, Thorsteinsson K, Rajan S, Lippert F, Folke F, Gislason G, et al. Bystander efforts and 1-year outcomes in out-of-hospital cardiac arrest. N Engl J Med. 2017;376(18):1737–47.CrossRefPubMed
5.
go back to reference Adielsson A, Hollenberg J, Karlsson T, Lindqvist J, Lundin S, Silfverstolpe J, Svensson L, Herlitz J. Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective. Heart. 2011;97(17):1391–6.CrossRefPubMed Adielsson A, Hollenberg J, Karlsson T, Lindqvist J, Lundin S, Silfverstolpe J, Svensson L, Herlitz J. Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective. Heart. 2011;97(17):1391–6.CrossRefPubMed
6.
go back to reference Neumar RW, Eigel B, Callaway CW, Estes NA 3rd, Jollis JG, Kleinman ME, Morrison LJ, Peberdy MA, Rabinstein A, Rea TD, et al. American Heart Association response to the 2015 Institute of Medicine Report on strategies to improve cardiac arrest survival. Circulation. 2015;132(11):1049–70.CrossRefPubMed Neumar RW, Eigel B, Callaway CW, Estes NA 3rd, Jollis JG, Kleinman ME, Morrison LJ, Peberdy MA, Rabinstein A, Rea TD, et al. American Heart Association response to the 2015 Institute of Medicine Report on strategies to improve cardiac arrest survival. Circulation. 2015;132(11):1049–70.CrossRefPubMed
7.
go back to reference van Diepen S, Girotra S, Abella BS, Becker LB, Bobrow BJ, Chan PS, Fahrenbruch C, Granger CB, Jollis JG, McNally B, et al. Multistate 5-year initiative to improve Care for out-of-Hospital Cardiac Arrest: primary results from the HeartRescue project. J Am Heart Assoc. 2017;6(9):e005716.CrossRefPubMedPubMedCentral van Diepen S, Girotra S, Abella BS, Becker LB, Bobrow BJ, Chan PS, Fahrenbruch C, Granger CB, Jollis JG, McNally B, et al. Multistate 5-year initiative to improve Care for out-of-Hospital Cardiac Arrest: primary results from the HeartRescue project. J Am Heart Assoc. 2017;6(9):e005716.CrossRefPubMedPubMedCentral
8.
go back to reference Reynolds JC, Lawner BJ. Management of the post-cardiac arrest syndrome. J Emerg Med. 2012;42(4):440–9.CrossRefPubMed Reynolds JC, Lawner BJ. Management of the post-cardiac arrest syndrome. J Emerg Med. 2012;42(4):440–9.CrossRefPubMed
9.
go back to reference Nolan JP, Soar J, Zideman DA, Biarent D, Bossaert LL, Deakin C, Koster RW, Wyllie J, Bottiger B. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary. Resuscitation. 2010;81(10):1219–76.CrossRefPubMed Nolan JP, Soar J, Zideman DA, Biarent D, Bossaert LL, Deakin C, Koster RW, Wyllie J, Bottiger B. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary. Resuscitation. 2010;81(10):1219–76.CrossRefPubMed
10.
go back to reference Hazinski MF, Nolan JP, Billi JE, Bottiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW, et al. Part 1: executive summary: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation. 2010;122(16 Suppl 2):S250–75.CrossRefPubMed Hazinski MF, Nolan JP, Billi JE, Bottiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW, et al. Part 1: executive summary: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation. 2010;122(16 Suppl 2):S250–75.CrossRefPubMed
11.
go back to reference Aufderheide TP, Lurie KG. Death by hyperventilation: a common and life-threatening problem during cardiopulmonary resuscitation. Crit Care Med. 2004;32(9 Suppl):S345–51.CrossRefPubMed Aufderheide TP, Lurie KG. Death by hyperventilation: a common and life-threatening problem during cardiopulmonary resuscitation. Crit Care Med. 2004;32(9 Suppl):S345–51.CrossRefPubMed
12.
go back to reference Falkenbach P, Kamarainen A, Makela A, Kurola J, Varpula T, Ala-Kokko T, Perttila J, Tenhunen J. Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest. Resuscitation. 2009;80(9):990–3.CrossRefPubMed Falkenbach P, Kamarainen A, Makela A, Kurola J, Varpula T, Ala-Kokko T, Perttila J, Tenhunen J. Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest. Resuscitation. 2009;80(9):990–3.CrossRefPubMed
13.
go back to reference Kety SS, Schmidt CF. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest. 1948;27(4):484–92.CrossRefPubMedPubMedCentral Kety SS, Schmidt CF. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest. 1948;27(4):484–92.CrossRefPubMedPubMedCentral
14.
go back to reference Brackett NC Jr, Cohen JJ, Schwartz WB. Carbon dioxide titration curve of normal man. Effect of increasing degrees of acute hypercapnia on acid-base equilibrium. N Engl J Med. 1965;272:6–12.CrossRefPubMed Brackett NC Jr, Cohen JJ, Schwartz WB. Carbon dioxide titration curve of normal man. Effect of increasing degrees of acute hypercapnia on acid-base equilibrium. N Engl J Med. 1965;272:6–12.CrossRefPubMed
16.
go back to reference Schneider AG, Eastwood GM, Bellomo R, Bailey M, Lipcsey M, Pilcher D, Young P, Stow P, Santamaria J, Stachowski E, et al. Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest. Resuscitation. 2013;84(7):927–34.CrossRefPubMed Schneider AG, Eastwood GM, Bellomo R, Bailey M, Lipcsey M, Pilcher D, Young P, Stow P, Santamaria J, Stachowski E, et al. Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest. Resuscitation. 2013;84(7):927–34.CrossRefPubMed
17.
go back to reference Roberts BW, Kilgannon JH, Chansky ME, Mittal N, Wooden J, Trzeciak S. Association between postresuscitation partial pressure of arterial carbon dioxide and neurological outcome in patients with post-cardiac arrest syndrome. Circulation. 2013;127(21):2107–13.CrossRefPubMed Roberts BW, Kilgannon JH, Chansky ME, Mittal N, Wooden J, Trzeciak S. Association between postresuscitation partial pressure of arterial carbon dioxide and neurological outcome in patients with post-cardiac arrest syndrome. Circulation. 2013;127(21):2107–13.CrossRefPubMed
18.
go back to reference Roberts BW, Kilgannon JH, Chansky ME, Trzeciak S. Association between initial prescribed minute ventilation and post-resuscitation partial pressure of arterial carbon dioxide in patients with post-cardiac arrest syndrome. Ann Intensive Care. 2014;4(1):9.CrossRefPubMedPubMedCentral Roberts BW, Kilgannon JH, Chansky ME, Trzeciak S. Association between initial prescribed minute ventilation and post-resuscitation partial pressure of arterial carbon dioxide in patients with post-cardiac arrest syndrome. Ann Intensive Care. 2014;4(1):9.CrossRefPubMedPubMedCentral
19.
go back to reference Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM. Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat. Pediatrics. 1995;95(6):868–74.PubMed Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM. Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat. Pediatrics. 1995;95(6):868–74.PubMed
20.
go back to reference Vaahersalo J, Bendel S, Reinikainen M, Kurola J, Tiainen M, Raj R, Pettila V, Varpula T, Skrifvars MB, FINNRESUSCI Study Group. Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurological outcome. Crit Care Med. 2014;42(6):1463–70. Vaahersalo J, Bendel S, Reinikainen M, Kurola J, Tiainen M, Raj R, Pettila V, Varpula T, Skrifvars MB, FINNRESUSCI Study Group. Arterial blood gas tensions after resuscitation from out-of-hospital cardiac arrest: associations with long-term neurological outcome. Crit Care Med. 2014;42(6):1463–70.
21.
go back to reference Eastwood GM, Schneider AG, Suzuki S, Peck L, Young H, Tanaka A, Martensson J, Warrillow S, McGuinness S, Parke R, et al. Targeted therapeutic mild hypercapnia after cardiac arrest: a phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation. 2016;104:83–90.CrossRefPubMed Eastwood GM, Schneider AG, Suzuki S, Peck L, Young H, Tanaka A, Martensson J, Warrillow S, McGuinness S, Parke R, et al. Targeted therapeutic mild hypercapnia after cardiac arrest: a phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation. 2016;104:83–90.CrossRefPubMed
22.
go back to reference Parke RL, McGuinness S, Eastwood GM, Nichol A, Nielsen N, Dankiewicz J, Bellomo R. Co-enrolment for the TAME and TTM-2 trials: the cerebral option. Crit Care Resusc. 2017;19(2):99–100.PubMed Parke RL, McGuinness S, Eastwood GM, Nichol A, Nielsen N, Dankiewicz J, Bellomo R. Co-enrolment for the TAME and TTM-2 trials: the cerebral option. Crit Care Resusc. 2017;19(2):99–100.PubMed
23.
go back to reference Mattsson N, Zetterberg H, Nielsen N, Blennow K, Dankiewicz J, Friberg H, Lilja G, Insel PS, Rylander C, Stammet P, et al. Serum tau and neurological outcome in cardiac arrest. Ann Neurol. 2017;82(5):665–75.CrossRefPubMedPubMedCentral Mattsson N, Zetterberg H, Nielsen N, Blennow K, Dankiewicz J, Friberg H, Lilja G, Insel PS, Rylander C, Stammet P, et al. Serum tau and neurological outcome in cardiac arrest. Ann Neurol. 2017;82(5):665–75.CrossRefPubMedPubMedCentral
24.
go back to reference Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206. Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med. 2013;369(23):2197–206.
25.
go back to reference Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, Cassan P, Coovadia A, D'Este K, Finn J, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa). Circulation. 2004;110(21):3385–97.CrossRefPubMed Jacobs I, Nadkarni V, Bahr J, Berg RA, Billi JE, Bossaert L, Cassan P, Coovadia A, D'Este K, Finn J, et al. Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries: a statement for healthcare professionals from a task force of the international liaison committee on resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Councils of Southern Africa). Circulation. 2004;110(21):3385–97.CrossRefPubMed
26.
go back to reference Brain Resuscitation Clinical Trial I Study Group. Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med. 1986;314(7):397–403.CrossRef Brain Resuscitation Clinical Trial I Study Group. Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. N Engl J Med. 1986;314(7):397–403.CrossRef
27.
28.
go back to reference Phelps R, Dumas F, Maynard C, Silver J, Rea T. Cerebral performance category and long-term prognosis following out-of-hospital cardiac arrest. Crit Care Med. 2013;41(5):1252–7.CrossRefPubMed Phelps R, Dumas F, Maynard C, Silver J, Rea T. Cerebral performance category and long-term prognosis following out-of-hospital cardiac arrest. Crit Care Med. 2013;41(5):1252–7.CrossRefPubMed
29.
go back to reference Blondin NA, Greer DM. Neurologic prognosis in cardiac arrest patients treated with therapeutic hypothermia. Neurologist. 2011;17(5):241–8.CrossRefPubMed Blondin NA, Greer DM. Neurologic prognosis in cardiac arrest patients treated with therapeutic hypothermia. Neurologist. 2011;17(5):241–8.CrossRefPubMed
30.
go back to reference Marshall A, Altman DG, Holder RL, Royston P. Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med Res Methodol. 2009;9:57.CrossRefPubMedPubMedCentral Marshall A, Altman DG, Holder RL, Royston P. Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med Res Methodol. 2009;9:57.CrossRefPubMedPubMedCentral
31.
go back to reference van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. J stat soft. 2011;45(3):67. van Buuren S, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. J stat soft. 2011;45(3):67.
32.
go back to reference Voicu S, Deye N, Malissin I, Vigue B, Brun PY, Haik W, Champion S, Megarbane B, Sideris G, Mebazaa A, et al. Influence of alpha-stat and pH-stat blood gas management strategies on cerebral blood flow and oxygenation in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest: a crossover study. Crit Care Med. 2014;42(8):1849–61.CrossRefPubMed Voicu S, Deye N, Malissin I, Vigue B, Brun PY, Haik W, Champion S, Megarbane B, Sideris G, Mebazaa A, et al. Influence of alpha-stat and pH-stat blood gas management strategies on cerebral blood flow and oxygenation in patients treated with therapeutic hypothermia after out-of-hospital cardiac arrest: a crossover study. Crit Care Med. 2014;42(8):1849–61.CrossRefPubMed
33.
go back to reference Eastwood GM, Suzuki S, Lluch C, Schneider AG, Bellomo R. A pilot assessment of alpha-stat vs pH-stat arterial blood gas analysis after cardiac arrest. J Crit Care. 2015;30(1):138–44.CrossRefPubMed Eastwood GM, Suzuki S, Lluch C, Schneider AG, Bellomo R. A pilot assessment of alpha-stat vs pH-stat arterial blood gas analysis after cardiac arrest. J Crit Care. 2015;30(1):138–44.CrossRefPubMed
34.
go back to reference Momiyama Y, Yamada W, Miyata K, Miura K, Fukuda T, Fuse J, Kikuno T. Prognostic values of blood pH and lactate levels in patients resuscitated from out-of-hospital cardiac arrest. Acute Med Surg. 2017;4(1):25–30.CrossRefPubMed Momiyama Y, Yamada W, Miyata K, Miura K, Fukuda T, Fuse J, Kikuno T. Prognostic values of blood pH and lactate levels in patients resuscitated from out-of-hospital cardiac arrest. Acute Med Surg. 2017;4(1):25–30.CrossRefPubMed
35.
go back to reference Maupain C, Bougouin W, Lamhaut L, Deye N, Diehl JL, Geri G, Perier MC, Beganton F, Marijon E, Jouven X, et al. The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest. Eur Heart J. 2016;37(42):3222–8.CrossRefPubMed Maupain C, Bougouin W, Lamhaut L, Deye N, Diehl JL, Geri G, Perier MC, Beganton F, Marijon E, Jouven X, et al. The CAHP (Cardiac Arrest Hospital Prognosis) score: a tool for risk stratification after out-of-hospital cardiac arrest. Eur Heart J. 2016;37(42):3222–8.CrossRefPubMed
36.
go back to reference Stammet P, Dankiewicz J, Nielsen N, Fays F, Collignon O, Hassager C, Wanscher M, Unden J, Wetterslev J, Pellis T, et al. Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 degrees C and 36 degrees C. Crit Care. 2017;21(1):153.CrossRefPubMedPubMedCentral Stammet P, Dankiewicz J, Nielsen N, Fays F, Collignon O, Hassager C, Wanscher M, Unden J, Wetterslev J, Pellis T, et al. Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33 degrees C and 36 degrees C. Crit Care. 2017;21(1):153.CrossRefPubMedPubMedCentral
Metadata
Title
Carbon dioxide dynamics in relation to neurological outcome in resuscitated out-of-hospital cardiac arrest patients: an exploratory Target Temperature Management Trial substudy
Authors
Florian Ebner
Matt B. A. Harmon
Anders Aneman
Tobias Cronberg
Hans Friberg
Christian Hassager
Nicole Juffermans
Jesper Kjærgaard
Michael Kuiper
Niklas Mattsson
Paolo Pelosi
Susann Ullén
Johan Undén
Matt P. Wise
Niklas Nielsen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2119-5

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