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Resuscitation 85 (2014) 332–335

Contents lists available at ScienceDirect

Resuscitation

j ourna l ho me pa g e: www.elsev ier .com/ locate / resusc i ta t ion

linical Paper

redicting the lack of ROSC during pre-hospital CPR: Should annd-tidal CO2 of 1.3 kPa be used as a cut-off value?�,��

eif Rognåsa,b,c,d,∗, Troels Martin Hansenc,d, Hans Kirkegaarde, Else Tønnesenf

Department of Research and Development, Norwegian Air Ambulance Foundation, P.O. Box 94, 1441 Drøbak, NorwayPre-hospital Critical Care Team, Department of Anaesthesiology, Viborg Regional Hospital, Heibergs Allé 4, 8800 Viborg, DenmarkPre-hospital Critical Care Team, Aarhus University Hospital, Oluf Palmes Allé 32, 8200 Aarhus N, DenmarkDepartment of Pre-hospital Medical Services, Central Denmark Region, Oluf Palmes Allé 34, 8200 Aarhus N, DenmarkCentre for Emergency Medicine Research, Aarhus University Hospital, Trøjborgvej 72-74, Building 30, 8200 Aarhus N, DenmarkDepartment of Anaesthesiology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus, Denmark

r t i c l e i n f o

rticle history:eceived 19 September 2013eceived in revised form4 November 2013ccepted 7 December 2013

eywords:ardiac arrestnd-tidal CO2

a b s t r a c t

Aim: The aim of this study was to investigate if an initial ETCO2 value at or below 1.3 kPa can be usedas a cut-off value for whether return of spontaneous circulation during pre-hospital cardio-pulmonaryresuscitation is achievable or not.Materials and methods: We prospectively registered data according to the Utstein-style template forreporting data from pre-hospital advanced airway management from February 1st 2011 to October 31st2012. Included were consecutive patients at all ages with pre-hospital cardiac arrest treated by eightanaesthesiologist-staffed pre-hospital critical care teams in the Central Denmark Region.Results: We registered data from 595 cardiac arrest patients; in 60.2% (n = 358) of these cases the pre-

re-hospital critical caremergency medical systemelicopter emergency medical systemritical decision making

hospital critical care teams performed pre-hospital advanced airway management beyond bag-maskventilation. An initial end-tidal CO2 measurement following pre-hospital advanced airway managementwere available in 75.7% (n = 271) of these 358 cases. We identified 22 patients, who had an initial end-tidalCO2 at or below 1.3 kPa. Four of these patients achieved return of spontaneous circulation.Conclusion: Our results indicates that an initial end-tidal CO2 at or below 1.3 kPa during pre-hospital CPRshould not be used as a cut-off value for the achievability of return of spontaneous circulation.

©

. Introduction

The European Resuscitation Council Guidelines for Resus-itations recommends the use of waveform capnography foronfirmation of tracheal tube placement whenever endotrachealntubation (ETI) is performed during cardio-pulmonary resuscita-ion (CPR).1

Several authors,2–8 most recently Heradstveit et al.9 andvigstad et al.,10 have suggested that measuring end-tidal car-on dioxide (ETCO2) may also be useful for optimising CPR quality

� A Spanish translated version of the abstract of this article appears as Appendixn the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.12.009.�� This is an open-access article distributed under the terms of the Creativeommons Attribution-NonCommercial-No Derivative Works License, which per-its non-commercial use, distribution, and reproduction in any medium, provided

he original author and source are credited.∗ Corresponding author at: Pre-hospital Critical Care Team, Aarhus Universityospital, Oluf Palmes Allé 32, 8200 Aarhus N, Denmark.

E-mail addresses: leifrogn@rm.dk (L. Rognås), troehans@rm.dk (T.M. Hansen),anskirk@rm.dk (H. Kirkegaard), else.toennesen@aarhus.rm.dk (E. Tønnesen).

300-9572/$ – see front matter © 2013 The Authors. Published by Elsevier Ireland Ltd. Alttp://dx.doi.org/10.1016/j.resuscitation.2013.12.009

2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.

and as an aid for prognostication during CPR. Kolar et al. from theemergency medical system (EMS) in Maribor, Slovenia found thatamong 1086 non-traumatic adult cardiac arrest patients (collectedduring a period of eight years) none of the patients in their studywith an initial ETCO2 below 1.33 kPa achieved ROSC.11 The authorssuggest using an ETCO2 of 1.33 kPa as a cut-off value for whetherreturn of spontaneous circulation (ROSC) following pre-hospitalcardiac arrest (CA) is achievable. We are not aware of any successfulvalidation of these findings and the knowledge of the prognosticsignificance of ETCO2 – measurements during pre-hospital CPRremains limited.

1.1. Objectives

The objective of the study was to investigate if an initial ETCO2value at or below 1.3 kPa can be used as a cut-off value for whetherROSC during pre-hospital CPR is achievable or not.

We hypothesised that in patients with pre-hospital CA,treated according to European Resuscitation Council Guidelines forResuscitation,1 an initial ETCO2 at or below 1.3 kPa is a predictorfor lack of ROSC and pre-hospital death.

l rights reserved.

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. Methods

.1. Study design

The data analysed in the present study is part of an observa-ional study12,13 where we prospectively collected data related tore-hospital advanced airway management (PHAAM) in accor-ance with the consensus-based template made by Sollid et al.14

.2. Setting

We investigated the anaesthesiologist-staffed pre-hospital crit-cal care teams in the Central Denmark Region. This region covers

mixed urban and rural area of approximately 13,000 km2 with aopulation of 1,270,000, and an overall population density is 97.7

nhabitants per km2.The standard EU emergency telephone number (1-1-2) covers

ll Denmark and there is an Emergency Medical Dispatch Centren each of the five Danish regions. Emergency Medical Dispatch isriteria based and telephone guided CPR is provided.15

The Emergency Medical Service (EMS) in the region is a two-iered system based on 64 road ambulances staffed by emergency

edical technicians (EMTs) supported by ten pre-hospital crit-cal care teams staffed with an anaesthesiologist (with at least½ years’ experience in anaesthesia) and a specially trained EMT.apid response vehicles deploy nine of the pre-hospital criticalare teams; the tenth team staffs a Helicopter Emergency Medicalervice (HEMS) helicopter.

The pre-hospital critical care teams covered by this studymploy approximately 90 anaesthesiologists as part time pre-ospital physicians. All pre-hospital critical care anaesthesiologists

n the region primarily work in one of the five regional emergencyospitals or at the university hospital and they all have in-hospitalmergency anaesthesia and advanced airway management bothn- and outside the operating theatre as part of their daily work.ntensive care is part of the Danish anaesthesiological curriculum.

EMTs and the pre-hospital critical care teams are expectedo follow the European Resuscitation Council Guidelines foresuscitation.1 The LUCAS® automated chest compression device

s available on all the anaesthesiologist-staffed rapid response vehi-les as well as on the HEMS. We have described the EMS system inur region in more detail elsewhere.12,13,16

We collected data between February 1st 2011 and Novemberst 2012.

.3. Participants

.3.1. Inclusion criteriaConsecutive pre-hospital cardiac arrest patients of all ages

here the pre-hospital critical care anaesthesiologist performedHAAM beyond bag-mask ventilation (BMV).

.4. Endpoints and variables

Primary endpoints were: (1) initial ETCO2 after PHAAM duringPR and (2) return of spontaneous circulation.

Secondary endpoints were: (1) Pre-hospital mortality.We defined initial ETCO2 as the first ETCO2 obtained after

HAAM and return of spontaneous circulation as any period (noime limit) of spontaneous circulation following PHAAM.

We collected all core data proposed in the consensus-basedemplate by Sollid et al. and we defined the variables as in thisemplate.14

The indications for performing PHAAM are categorised by Sollidt al.14 We included patients where the pre-hospital critical carehysician had marked “cardiac arrest” as the reason for performingHAAM.

n 85 (2014) 332–335 333

The pre-hospital critical care teams or the EMTs on the roadambulances measured oxygen saturation, heart rate and bloodpressure by using a LifePak 12 monitor (Physio-Control, Redmond,USA). The pre-hospital critical care teams monitored ETCO2 eithervia the LifePak 12 or via a Nellcor NPB-75 capnograph (Tyco Health-care Group LP, Pleasanton, USA). None of these devices can displaythe ETCO2 as 1.33 kPa; it is either 1.3 or 1.4. Therefore, we chose ator below 1.3 kPa as the cut-off value in this study.

The physicians registered the initial ETCO2 as a free-text vari-able. During data analysis, we labelled the initial ETCO2 as beingeither under 1.3 kPa, at 1.3 kPa or above 1.3 kPa.

2.5. Data sources and data collection

We collected data from eight of the ten pre-hospital criticalcare teams, including the HEMS. Due to substantial differences instaffing, caseload, case mix and routines during the study period,only eight of the ten pre-hospital critical care teams provided datafor the study.

The anaesthesiologists filled in a registration form (provided asa Supplemental File) containing all the core data recommended bySolid et al.14 If the patient died on-scene, we reviewed the writ-ten pre-hospital charts as well as the entry made in the electronicpatient journal for any evidence of temporary ROSC. For patientstransported during ongoing CPR, we evaluated the same sourcesfor evidence of temporary ROSC. If there were any doubt, whetherthe patient achieved ROSC or not we included the patient in the “noROSC” group during data analysis.

2.6. Bias

To reduce the risk of recall bias and selection bias, the primaryinvestigator reviewed the registration forms on a day-to-daybasis. We crosschecked the registration forms with the standardpre-hospital records from the pre-hospital critical care teams toensure the highest possible data coverage. In cases of missing dataor inconsistencies, we asked the attending pre-hospital criticalcare physician to provide additional details for clarification.

2.7. Study size and statistical methods

In-depth discussions with an expert statistician at Aarhus Uni-versity resulted in the following:

In theory, it would only take one single patient with a true initialETCO2 at or below 1.3 kPa and subsequent ROSC for us to have toreject the hypothesis. However, this one case could be due to forinstance equipment malfunction and we therefore decided that wewould reject the hypothesis if two or more patients with an initialETCO2 at or below 1.3 kPa achieved ROSC.

Sample size calculations made by the statistician in the sta-tistical software Stata 12 (StataCorpLP) showed that to be able toconfirm the hypothesis with a power of at least 80% and a levelof significance of 95% we would need to include 100 patients withan ETCO2 of less than 1.3 and no ROSC. In cases of unobtainablemissing data, we performed complete case analyses.

2.8. Ethics

No patients had their treatment altered because of the study.All physicians participated in the study on a voluntary basis –

there were no refusals.The study did not involve any alterations from normal practice

and according to Danish law, it did not need the approval of theRegional Ethics Committee, nor did we need the patients’ consentto register and publish the data. The Danish Data Protection Agencyapproved the study (Journal number 2013-41-1462).

334 L. Rognås et al. / Resuscitatio

Table 1Demographic data.

Numbers %

Total patients included (N) 358Age (years) mean 63.1 0–97 (range)Age < 16 years 11 3.1Age < 2 years 6 1.7Males 232 64.8ASA-PSa-score mean 2.32 1–4 (range)Pre-existing cardiac disease 96 26.8Pre-existing hypertension 29 8.1Pre-existing COPDb 40 11.2Pre-existing diabetes 18 5.0Pre-existing neurological disease 23 6.4Other pre-existing disease 99 27.7Traumatic cardiac arrest 32 8.9

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a American Society of Anesthesiologists Physical Performance.b Chronic obstructive pulmonary disease.

. Results

.1. Participants

During the 21 months, the participating pre-hospital criticalare teams treated 24 693 patients. The teams registered data from081 PHAAM cases corresponding to 93.3% of PHAAM patients.atients in CA accounted for 55.0% (n = 595) of these cases. The pre-ospital critical care physicians performed PHAAM beyond BMV on0.2% (n = 358) of the 595 patients in CA; the rest were treated withag-mask ventilation and in these cases ETCO2 were not routinelyeasured. In 97.8% (n = 350) of the 358 cases the anaesthesiolo-

ists performed PHETI, in 2.0% (n = 7) they inserted an SAD and inne case a surgical airway (SAW) were needed. These 358 PHAAMatients were included in the current study.

.2. Descriptive data

Table 1 displays demographic data of the 358 CA patients treatedith PHETI/SAD/SAW.

.3. Main results

An initial ETCO2 was available in 271 of the CA cases.Among these 271 cases, we identified 22 patients, who had an

nitial ETCO2 after PHAAM below 1.3 kPa; additional seven patientsad an initial ETCO2 = 1.3 kPa.

Three patients with an initial ETCO2 below 1.3 kPa and oneatient with an initial ETCO2 of 1.3 kPa achieved ROSC. We describehese four patients in detail in Table 2.

. Discussion

.1. Main results

Based on an retrospective analysis of over 700 pre-hospital car-iac arrest patients Kolar et al. suggests an initial ETCO2 of less than.33 kPa as a cut-off value to identify patients who will not achieveOSC.11 Our results cannot confirm their findings. We identified

our CA patients with an initial ETCO2 at or below 1.3 kPa who allchieved ROSC, and our hypothesis that an initial ETCO2 at or below.3 kPa during pre-hospital CPR can be used as a predictor of pre-ospital death, must therefore be rejected. It is unlikely that all fourardiac arrest cases who achieved ROSC following an initial ETCO2

f 1.3 kPa or less should have experienced a falsely low ETCO2 value.

The results published by Callaham et al. support our findings.17

hey investigated 55 patients in CA and found that four of thoseith an initial ETCO2 below 1.3 kPa achieved ROSC.

n 85 (2014) 332–335

In a study of 575 Norwegian pre-hospital cardiac arrest patientstreated by physician-staffed HEMS, Heradstveit et al., 9 found manyconfounding factors complicating the interpretation of ETCO2monitoring during CPR. The authors could not identify a “clear gen-eralised cut-off value determining whether ROSC would be achievedor not”. Our results seem to support this view.

In our opinion, ETCO2 monitoring during CPR provides impor-tant information but the results of the current study does not allowus to support the use of an initial ETCO2 at or below 1.3 as a cut-off value for the achievement of ROSC in pre-hospital CA patients.Basing the decision of whether or not to terminate CPR on this cut-off value may diminish patients’ safety and impair patient outcomefollowing pre-hospital CA.

We advocate the use of ETCO2 measurements as one parameteramong others (such as the result of focused ultrasound assessment)to guide the critical decision-making during pre-hospital CPR.

4.2. Limitations

The study was designed according to the Utstein-style templatefor reporting data from pre-hospital advanced airway managementby Sollid et al.,14 and not according to the template for repor-ting data from pre-hospital cardiac arrest.18 Consequently, readersshould interpret the non-airway management related results in thecurrent study with caution.

We measured the ETCO2 values on one of the two portablecapnographs and we did not routinely check the readings by mea-surement of ETCO2 on both capnographs or by measuring thepartial pressure of CO2 in arterial blood. Never the less, our wayof measuring ETCO2 depicts daily clinical practice.

The 23% lacking measurements of ETCO2 is a potential sourceof bias. We do not know the reason for these missing data. Itcould be because of equipment malfunction or unavailable equip-ment due to maintenance. It could also be because the attendinganaesthesiologist chose not to use capnography, which is not inadherence with current guidelines.1 However, the missing datadoes not change the fact that four patients with an initial ETCO2 ator below 1.3 kPa achieved ROSC and it does therefore not influenceour conclusion. In a more general perspective, our findings indicatea need for an increased use of ETCO2- measurements during CPR inour service.

We did not design this study to investigate the different factorsinfluencing ETCO2 during CPR and our results are merely an attemptto investigate the use of an initial ETCO2 at or below 1.3 kPa as a cut-off value in the critical decision making process during pre-hospitalCPR in a non-selected population of pre-hospital CA patients.

Survival beyond survival to admission was outside the scope ofthis study. This is in coherence with the paper by Kolar et al.11

The attending anaesthesiologists registered all the data. Theyare therefore potentially subject to registration bias (systematicerrors in the registration of data) or recall bias. The high capturerate reduces the risk of selection bias. Based on the day-to-daycrosscheck of the registration forms against both the writtenpre-hospital journals and the compulsory entries made by theanaesthesiologists in the patients’ hospital records, the extent ofselection bias is probably limited.

4.3. Generalisability

This was a study from one homogenous Danish system ofanaesthesiologist-staffed pre-hospital critical care teams. This lim-its the ability to generalise the findings to other systems with

different staffing, caseload or case mix. Never the less, treatmentwere according to current guidelines and we believe that our resultscan be of use to other physician-staffed as well as paramedic-staffedpre-hospital services performing pre-hospital advanced airway

L. Rognås et al. / Resuscitation 85 (2014) 332–335 335

Table 2Patients with return of spontaneous circulation after an initial ETCO2 ≤ 1.3 during CPR.a

Sex Age (years) ASA-PSb score Pre-existing disease Type of cardiac arrest First ECG First ETCO2 (kPa) ETCO2 (kPa) in the EDc Spontaneous circulationin the ED

Fd 74 2 None Medical Sinus rhythme 1.1 1.3 YesF 84 2 Other Medical PEAf 0.8 3.3 YesMg 79 3 Cardiac + other Medical Unknown 1.3 8.0 YesM 72 2 Cardiac Medical VF 1.2 2.5 Noh

a Cardio-pulmonary resuscitation.b American Society of Anesthesiologists Physical Performance.c Emergency department.d Female.e Ventricular fibrillation occurred after arrival of the Emergency Medical Services.

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anagement with ETCO2 monitoring during pre-hospital cardiacrrest.

.4. Perspectives

Further research is needed to confirm or reject the existence of aniversal cut-of value of ETCO2 for the achievement of ROSC duringre-hospital CPR. Based on our results, we find it doubtful whetheruch a value does exist.

. Conclusion

In this study of 271 pre-hospital cardiac arrest patients treatedith pre-hospital advanced airway management other than bag-ask ventilation by pre-hospital critical care anaesthesiologists,e identified four patients with an initial ETCO2 at or below 1.3 kPaho achieved return of spontaneous circulation. Our results can-ot confirm the hypothesis that an initial ETCO2 at or below 1.3 kPa

ound during pre-hospital CPR is a predictor for the lack of returnf spontaneous circulation. We advise against using our results toiscard the use of ETCO2 measurements as one important param-ter among several in the critical decision making process duringre-hospital CPR.

onflict of interest statement

The authors declare that they have no conflict of interests.

cknowledgements

The Norwegian Air Ambulance Foundation, The Laerdal Founda-ion for Acute Medicine and The Central Denmark Region, foundedhe study by sponsoring the salary of LR.

TMH, HK and ET were funded by their departments.The sponsors have had no influence on study design, data collec-

ion, data analysis and interpretation, the writing of the manuscriptr the decision to submit the paper for publication.

The authors wish to thank all the pre-hospital critical care physi-ians who collected the data and all the EMTs who reminded themo do so.

A special thanks to EMT Tinna Højmose Østergaard for hernvaluable assistance in all the practicalities of the data collection.

ppendix A. Supplementary data

Supplementary data associated with this article can be found,n the online version, at http://dx.doi.org/10.1016/j.resuscitation.013.12.009.

mated chest compression device.

References

1. Nolan JP, Soar J, Zideman DA, et al. European Resuscitation Council Guide-lines for Resuscitation 2010. Section 1. Executive summary. Resuscitation2010;81:1219–76.

2. Ahrens T, Schallom L, Bettorf K, et al. End-tidal carbon dioxide measurementsas a prognostic indicator of outcome in cardiac arrest. Am J Crit Care 2001;10:391–8.

3. Dubin A, Murias G, Estenssoro E, et al. End-tidal CO2 pressure deter-minants during hemorrhagic shock. Intensive Care Med 2000;26:1619–23.

4. Grmec S, Krizmaric M, Mally S, Kozelj A, Spindler M, Lesnik B. Utstein styleanalysis of out-of-hospital cardiac arrest–bystander CPR and end expired carbondioxide. Resuscitation 2007;72:404–14.

5. Morimoto Y, Kemmotsu O, Morimoto Y, Gando S. End-tidal carbon dioxide andresuscitation. Curr Opin Anaesthesiol 1999;12:173–7.

6. Salen P, O’Connor R, Sierzenski P, et al. Can cardiac sonography and capnographybe used independently and in combination to predict resuscitation outcomes?Acad Emerg Med 2001;8:610–5.

7. Sanders AB, Ewy GA, Bragg S, Atlas M, Kern KB. Expired PCO2 as a progno-stic indicator of successful resuscitation from cardiac arrest. Ann Emerg Med1985;14:948–52.

8. Sanders AB, Kern KB, Otto CW, Milander MM, Ewy GA. End-tidal carbon dioxidemonitoring during cardiopulmonary resuscitation. A prognostic indicator forsurvival. J Am Med Assoc 1989;262:1347–51.

9. Heradstveit BE, Sunde K, Sunde GA, Wentzel-Larsen T, Heltne JK. Factorscomplicating interpretation of capnography during advanced life support incardiac arrest – a clinical retrospective study in 575 patients. Resuscitation2012;83:813–8.

0. Qvigstad E, Kramer-Johansen J, Tomte O, et al. Clinical pilot study of differenthand positions during manual chest compressions monitored with capnogra-phy. Resuscitation 2013;84:1203–7.

1. Kolar M, Krizmaric M, Klemen P, Grmec S. Partial pressure of end-tidal car-bon dioxide successful predicts cardiopulmonary resuscitation in the field: aprospective observational study. Crit Care 2008;12:R115.

2. Rognas L, Hansen TM, Kirkegaard H, Tonnesen E. Pre-hospital advanced air-way management by experienced anaesthesiologists: a prospective descriptivestudy. Scand J Trauma Resusc Emerg Med 2013;21:58.

3. Rognas L, Hansen TM, Kirkegaard H, Tonnesen E. Refraining from pre-hospitaladvanced airway management: a prospective observational study of criti-cal decision making in an anaesthesiologist-staffed pre-hospital critical careservice. Scand J Trauma Resusc Emerg Med 2013;21:75.

4. Sollid SJ, Lockey D, Lossius HM. A consensus-based template for uniform repor-ting of data from pre-hospital advanced airway management. Scand J TraumaResusc Emerg Med 2009;17:58.

5. Andersen MS, Johnsen SP, Sorensen JN, Jepsen SB, Hansen JB, Christensen EF.Implementing a nationwide criteria-based emergency medical dispatch sys-tem: a register-based follow-up study. Scand J Trauma Resusc Emerg Med2013;21:53.

6. Rognas LK, Hansen TM. EMS-physicians’ self reported airway management train-ing and expertise; a descriptive study from the Central Region of Denmark. ScandJ Trauma Resusc Emerg Med 2011;19:10.

7. Callaham M, Barton C. Prediction of outcome of cardiopulmonary resuscita-tion from end-tidal carbon dioxide concentration. Crit Care Med 1990;18:358–62.

8. Jacobs I, Nadkarni V, Bahr J, et al. Cardiac arrest and cardiopulmonary resus-citation outcome reports: update and simplification of the Utstein templatesfor resuscitation registries, A statement for healthcare professionals from a task

force of the international liaison committee on resuscitation (American HeartAssociation, European Resuscitation Council, Australian Resuscitation Council,New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada,InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).Resuscitation 2004;63:233–49.