Resuscitation Today Autumn 2016 by Media Publishing Company

Volume 3 No. 3

Autumn 2016

Resuscitation Today A Resource for all involved in the Teaching and Practice of Resuscitation Supported by CPRO

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In this issue Evidence - Barriers in the Implementation of The Resuscitation Guidelines Evidence - Opening the Door to Researching A&E www.i-gel.com

Quality, innovation and choice www.intersurgical.co.uk

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CONTENTS

CONTENTS 4

EDITORS COMMENT

EDUCATION

EVIDENCE

NEWS

Resuscitation Today This issue edited by: David Halliwell MSc Paramedic Flfl c/o Media Publishing Company Media House 48 High Street SWANLEY, Kent BR8 8BQ ADVERTISING & CIRCULATION: Media Publishing Company Media House, 48 High Street SWANLEY, Kent, BR8 8BQ Tel: 01322 660434 Fax: 01322 666539 E: info@mediapublishingcompany.com www.MediaPublishingCompany.com PUBLISHED: Spring, Summer and Autumn COPYRIGHT: Media Publishing Company Media House 48 High Street SWANLEY, Kent, BR8 8BQ

COVER STORY i-gel® single use supraglottic airway from Intersurgical i-gel® is the second generation supraglottic airway of choice in many hospitals in Europe and around the world. Indicated for use in resuscitation in adults, i-gel is easy and rapid to insert and is consistently reliable – in many cases, insertion can be achieved in less than five seconds1. The device incorporates a gastric channel for improved safety, an integral bite block to reduce the possibility of airway occlusion and a buccal cavity stabiliser to aid rapid insertion and reduce the potential for rotation. Low post-operative complications and high seal pressures provide benefits to both clinician and patient2. A number of case reports and clinical studies have highlighted the potential advantages i-gel® offers in the resuscitation scenario3,4,5,6, where seconds can make all the difference.

You can find more information about the Intersurgical i-gel® range at: www.i-gel.com Choose Intersurgical for Quality, Innovation and Choice. Contact information: Intersurgical, Crane House, Molly Millars Lane, Wokingham, Berkshire RG41 2RZ, England. Tel: 0118 9656 300 Fax: 0118 9656 356 Email: info@intersurgical.co.uk Website: www.intersurgical.co.uk References: Bamgbade OA, Macnab WR, Khalaf WM: Evaluation of the i-gel airway in 300 patients. Eur J Anaesthesiol. 2008 Oct;25(10):865-6. Richez B, Saltel L, Banchereau F, Torrielli, Cros AM: A new single use supraglottic airway with a noninflatable cuff and an esophageal vent: An observational study of the i-gel: Anesth Analg. 2008 Apr;106(4):1137-9. 3 Gatward JJ, Thomas MJC, Nolan JP, Cook TM: Effect of chest compressions on the time taken to insert airway devices in a manikin: Br J Anaesth. 2008 Mar;100(3):351-6 4 Gabbott DA, Beringer R: The i-gel supraglottic airway: A potential role for resuscitation?: Resuscitation. 2007 Apr;73(1):161-2. 5 Soar J: The i-gel supraglottic airway and resuscitation - some initial thoughts: Resuscitation. 2007 Jul;74(1):197. 6 UK Resuscitation Council Advanced Life Support Guide (5th Edition). Revised June 2008. 1 2

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The most recent addition to the i-gel range is the i-gel O2 Resus Pack. The i-gel O2 has been specially designed to facilitate ventilation as part of standard resuscitation protocols, such as those designated by the European Resuscitation Council (ERC). However, the i-gel O2 also incorporates a supplementary oxygen port for the delivery of passive oxygenation, or Passive Airway Management (PAMTM), as part of an appropriate Cardio Cerebral Resuscitation (CCR) protocol.

PUBLISHERS STATEMENT: The views and opinions expressed in this issue are not necessarily those of the Publisher, the Editors or Media Publishing Company.

EDITORS COMMENT

EDITORS COMMENT Welcome to another issue of Resuscitation Today. In this issue we continue our pursuit of reviewing themes of education, evidence and equipment. We take a look at some of the barriers to implementing the 2015 resuscitation guidelines, and find some interesting results across Europe. Indeed, from my own time spent in Europe, what one might consider “standard practice” in Ireland and the UK can vary quite dramatically as one travels across the continent. It is important to identify these barriers and work towards a common standard, affording all patients the same quality of care.

RESUSCITATION TODAY - AUTUMN 2016

“From my own time spent in Europe, what one might consider “standard practice” in Ireland and the UK can vary quite dramatically as one travels across the continent.”

We investigate POC lactate measurements in trauma, and the use of NIRS during resuscitation – tools which are now making an appearance across various clinical settings, in-hospital and prehospital alike. Continued studies of these adjuncts will lend credence to their inclusion (or indeed exclusion) in resuscitation programmes of the future. We hope you enjoy this issue, and as always, if you have an article or an idea for submission for upcoming issues, please feel free to contact us info@mediapublishingcompany.com.

Until next time, Alan Batt Editor

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EDUCATION

BARRIERS IN THE IMPLEMENTATION OF THE RESUSCITATION GUIDELINES: EUROPEAN SURVEY OF DEFIBRILLATION TECHNIQUES Paweł Krawczyk1, Andrzej A. Kononowicz2 and Janusz Andres1 Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2016 24:28

Abstract

Conclusions

Background

There are limitations and barriers in the implementation of the

The European Resuscitation Council (ERC) Guidelines recommend providing chest compressions during defibrillator charging and using adhesive pads for defibrillation to increase the effectiveness of resuscitation. However, the most common defibrillation technique in each European country is unknown, as are the potential barriers in implementation of the guidelines. The aim of this study was to assess the techniques of defibrillation procedures performed by professional European healthcare providers and to estimate how frequently adhesive pads are used.

Methods We sent an online questionnaire to the ERC National Representatives that contained 12 questions regarding the techniques of defibrillation and monitoring heart rhythm during cardiac arrest. We also evaluated the frequency and indications of manual paddles use.

Results

defibrillation technique guidelines. There are still countries where the use of adhesive pads is low due to economic and traditional reasons. There is a need for further efforts focused on guidelines implementation.

Keywords Defibrillation, Technique, Adhesive pads, Manual paddles, Cardiopulmonary resuscitation, Advanced life support, Monitoring, Coupling medium

Background Performing defibrillation when a shockable rhythm has been identified is one of the key interventions of cardiac arrest with clearly proven benefits influencing patient survival [1]. The likelihood of a successful defibrillation attempt is lower not only when the procedure is done too late [2, 3], but also when there is a delay between stopping chest compressions and shock delivery [4, 5, 6]. A pause longer than 5–10 s may influence defibrillation effectiveness [7]. The European Resuscitation Council (ERC) Guidelines [1] recommend providing chest compressions during defibrillator charging to eliminate unnecessary breaks in chest

RESUSCITATION TODAY - AUTUMN 2016

We collected questionnaires from 27 out of 33 invited ERC member

compressions and to decrease the time between the stopping of CPR

countries. The response rate was 82 %. Seventeen (17/27; 63 %)

and shock delivery. The guidelines also recommend the use of adhesive

declared the use of adhesive pads. The leading cause for not using

pads for defibrillation. This has the potential to make the procedure

adhesive pads was economic reason (9/17; 53 %). Some respondents

quicker, safer and more effective than with manual paddles [8, 9, 10]. The

declared resistance to using adhesive pads by healthcare providers

ERC Guidelines for Resuscitation 2015 recognize that defibrillator paddles

or tradition connected with manual paddles use. We found three

are used in some settings [1]. The use of paddles is still common in many

leading techniques of defibrillation with manual paddles: Charging

European countries [11, 12, 13], however, it is not known what the most

paddles keeping them on the defibrillator during chest compressions

common defibrillation technique is in each country or what the potential

being delivered (9/21; 43 %), Charging paddles keeping them on the

barriers in implementation of the guidelines are.

patient chest during chest compressions being delivered (6/21; 29 %), Charging paddles on the patient chest without chest compressions

This paper provides information regarding the technique of defibrillation

(5/21; 24 %). Respondents from 11 countries declared the use of gel or

procedures carried out by professional European healthcare providers

electrode pastes during defibrillation with manual paddles.

in both pre- and in-hospital cardiac arrests. It also indicates the barriers in implementation of the guidelines regarding the use of adhesive pads.

Discussion

Methods

This study collected preliminary data showing how defibrillation is performed in Europe. It revealed the recommeded techniques underuse

In January 2016, we sent an e-mail with invitation to participate in the online

and identyfied barriers in the Resuscitation Guidelines implementation.

survey [14] to all ERC National Representatives – one per each member

The survey should be open to a wider group of respondents. in each

country. The questionnaire contained 12 questions regarding the technique

country in future.

of defibrillation and how heart rhythm is monitored during cardiac arrest.

EDUCATION Additional questions were asked in regard to manual paddles

adhesive pads by healthcare providers or a tradition connected with

use (indications, coupling medium usage, technique of manual

using manual paddles. In cases of using manual paddles, 7/23 (30 %)

defibrillation). The study questionnaire was created based on results

respondents declared use of gel and 4/23 (17 %) electrode pastes as

and conclusions of the previous studies [11, 12, 13] and after consulting

a coupling medium and 48 % (11/23) used gel pads. In the free text

it with the then ERC Director of Science and Research. In case of no

comments, some respondents declared a problem with the availability

response within one week we sent up to 3 reminders. When still not

of gel pads in their country.

successful we sent the invitation to the missing national resuscitation councils’ secretariat or second contact person if available.

Results We collected questionnaires from 27 out of 33 ERC member countries: Austria, Belgium, Croatia, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Hungary, Iceland, Italy, Luxembourg, Malta, Norway, the Netherlands, Poland, Romania, Russian Federation, Serbia,

We found three leading techniques of manual defibrillation with paddles (21 responses): A. Charging paddles keeping them on the defibrillator during chest compressions being delivered (9/21; 43 %) B. Charging paddles keeping them on the patient’s chest during chest compressions being delivered (6/21; 29 %)

Slovakia, Slovenia, Sweden, Switzerland, Turkey, Tunisia and the United Kingdom. The following countries did not respond: Bosnia and Herzegovina, Egypt, Portugal, Spain, Sudan and United Arabic Emirates

C. Charging paddles on the patient chest without chest compressions (5/21; 24 %)

(Fig. 1). The response rate was 82 %. The respondents were physicians (24/27; 89 %), two nurses and a paramedic. Most of the respondents

As a free text comment, one respondent stated that “there was no

worked in a hospital only (13/27; 48 %), both in- and out-of-hospital

uniform practice”.

worked 8/27 (30 %) and 6/27 (22 %) worked outside of the hospital only. The respondents judged the benefits of the chosen defibrillation Sixty-three percent of the respondents (17/27) declared using adhesive

technique with manual paddles selecting high chest compression

pads as the defibrillation technique. In the opinion of the respondents

quality during charging paddles in 7/17 (41 %), a short time from chest

adhesive pads are used more often in pre-hospital cardiac arrest than

compression cessation to shock delivery in 5/17 (29 %), and safety of

in-hospital (the frequency of use 76–100 % was estimated for pre-

the rescuer in 2/17 (12 %) of responses.

hospital 16/27 (59 %) vs. in-hospital 10/27 (37 %)). Figure 1 presents responses regarding the technique of defibrillation used pre-hospital

Cardiac arrest rhythm was initially assessed using adhesive pads by

and in-hospital. There were 10/27 (37 %) countries declaring use of

15/27 (56 %) of respondents, 6/27 (22 %) declared use of the quick-

adhesive pads in both pre- and in-hospital environment in a rate of

look technique for that purpose and 5/27 (19 %) preferred 3-lead ECG

76–100 %. The leading cause indicated by respondents for not using

for initial monitoring of cardiac arrest. As a free text comment, one

adhesive pads in their country was for economic reasons 9/14 (64 %).

respondent stated that “there was no standard practice, depending on

Three (3/14; 21 %) respondents declared a resistance to the use of

people involved and equipment available”.

RESUSCITATION TODAY - AUTUMN 2016

Fig. 1 Responses on technique of defibrillation used in pre-hospital and in-hospital areas

EDUCATION The detailed resultsofofthe thisdefibrillation part of the survey are available in Table Table 1 Results techniques survey 2016.1.

Questions 1-9 Table 1 Results of the defibrillation techniques survey 2016. # Question Response n % Questions 1-9 1. How do you usually perform # defibrillation Question Response in your department/working place: 1. How do you usually perform defibrillation in your adhesive pads department/working place: manual paddles adhesive pads 2. What do you estimate is the percentagemanual of usingpaddles adhesive pads in your 2. What do you country: estimatePre-hospital is the percentage76–100 of using % adhesive pads in your country: Pre-hospital 51–75 % 76–100 % 26–50 % 51–75 % 6–25 % 26–50 % 0–5 % 6–25 % 3. What do you estimate is the percentage of 0–5 % using adhesive pads in your country: In-hospital 3. What do you estimate 76–100 % is the percentage of using adhesive pads in your country: In-hospital 51–75 % 76–100 % 26–50 % 51–75 % 6–25 % 26–50 % 0–5 % 6–25 % 4. If adhesive pads use in your country is % % please specify the lower than0–5 76–100 reasonpads for that 4. main If adhesive use in your country is lower thanEconomic 76–100 % reasons please specify the main reason for that Resistance to use adhesive Economic reasons providers pads by healthcare Resistance to use adhesive Other, please specify in box pads by healthcare next to the questionproviders

RESUSCITATION TODAY - AUTUMN 2016

Other, please do specify 5. What coupling medium you in box next to the question use in order to facilitate manual with paddles your country? 5. defibrillation What coupling medium doinyou use in orderElectrode to facilitate manual pastes defibrillation with paddles in your country? Gel Electrode pastes Gel pads Gel Other Gel pads 6. If you are using manual paddles Otherof defibrillation what technique is preferred in your country 6. If you are using manual paddles what technique of defibrillation Charging paddles keeping is preferredthem in your on country the defibrillator

N = 27 % N = 27

17 63 % 10 37 % 17 63 % N = 27 10 37 % N = 27 16 59 % 2 16 1 2 4 1 4 4 4

7% 59 % 4% 7% 15 % 4% 15 % 15 % N = 27 15 %

10 N 37=%27 4 10 2 4 5 2 6 5 6

15 % 37 % 7% 15 % 19 % 7% 22 % 19 % N = 14 22 % N = 14

Table 1 Results of the defibrillation techniques survey 2016. Questions 1-9 (Continued) Table 1 Results of the defibrillation techniques survey 2016. chest compressions quality 7 41 % Questions 1-9High (Continued) delivered during charging paddles High Safetychest - no compressions risk for rescuerquality delivered during charging paddles Short time from chest compressions Safety - notorisk for rescuer cessation shock delivery Short time from chest Other (please specify) compressions cessation to shock delivery 8. What major drawback of other defibrillation (please specify) techniquesOther with paddles make them useless for you 8. What majorDelay drawback of other defibrillation from chest compressions techniquescessation with paddles makedelivery them useless for you to shock

41 12 % %

5 2

29 % 12 %

29 18 % %

N = 20 18 %

N 40=%20

40 20 % %

Poor chest compressions quality Risk for rescuer delivered during charging paddles Other (please specify) Risk for rescuer 9. If healthcare providers in your country use Other (please specify) the quick-look with manual paddles technique the FIRST providers assessment cardiac arrest 9. for If healthcare in in your country usevictim, what would bewith the next steppaddles when confirming the quick-look manual technique shockable rhythm for the FIRST assessment in cardiac arrest victim, what wouldCharge be thethe next step whenwith confirming defibrillator paddles shockable rhythm ON the patient chest WITH ongoing

20 35 % %

1 7

5% 35 % N = 16 5%

13 %

chest Chargecompressions the defibrillator with paddles ON the patient chest WITH Charge the defibrillator withongoing paddles chest compressions ON the patient chest WITHOUT chest

13 %

31 %

compressions Charge the defibrillator with paddles ON the patient chest Remove paddleschest fromWITHOUT the patient chest compressions and resume/start chest compressions,

31 %

25 %

Delay from compressions chest compressions Poor chest quality cessation shockcharging deliverypaddles delivered to during

64 %

3 9

21 % 64 %

21 14 % %

than deliver shockfrom afterthe charging Remove paddles patient chest defibrillator and resume/start chest compressions, than shockplease after charging Otherdeliver technique, describe in defibrillator box on the right hand side

14 N =%23

Other technique, please describe in box on the right hand side

N = 16

When the quick-look technique was used and shockable rhythm was

N = 23

detected, the next suggested step from 2/16 (13 %) of respondents was

17 %

charging the defibrillator with the paddles on the patient’s chest with

7 4 11 7 1 11

30 % 17 % 48 % 30 % 4% 48 % N = 21 4%

N = 21

ongoing chest compressions, however 5/16 (31 %) of respondents declared charging the defibrillator with paddles on the patient’s chest without chest compressions. Five out of 16 (31 %) of respondents suggested removing the paddles from the patient’s chest and resuming/starting chest compressions, and then delivering a shock after charging the defibrillator. The technique for further monitoring of cardiac arrest rhythm and the modification of the monitoring in case of low ECG signal quality is shown in Table 2.

43 %

during chest compressions Charging paddles keeping being delivered them on the defibrillator during chest compressions Charging paddles keeping being delivered them on the patient chest

43 %

In free text comments regarding the technique of monitoring cardiac rhythm,

29 %

changing ECG leads may be a solution for poor ECG signal quality and that

during chest compressions Charging paddles keeping being delivered them on the patient chest during chest compressions Charging paddles on the patient being deliveredchest compressions chest without

29 %

24 %

Discussion

24 5 %%

The Resuscitation Guidelines recommend minimizing unnecessary

N = 17 5%

Charging paddles(please on thedescribe): patient Other technique chest without chest compressions 7. What major benefit of chosen manual defibrillation Otherpaddles technique describe): technique with you(please find useful 7. What major benefit of chosen manual defibrillation technique with paddles you find useful

N = 17

there were suggestions that adhesive pads provide a good ECG signal, that more modern equipment will result in a better quality of ECG.

breaks in chest compression delivery [1]. When defibrillation is attempted, the time from cessation of chest compressions to shock delivery should not exceed 5–10 s, which is possible if chest compressions are performed while charging the defibrillator.

EDUCATION Table 2 The way of monitoring cardiac arrest rhythm. Results of the defibrillation techniques survey 2016. Questions 10–12 #

Adhesive pads

“Quick look” with paddles

3-lead ECG

Other

No change in monitoring technique

10. Cardiac arrest rhythm initial assessment

56 % (15/ 27)

22 % (6/27)

19 % (5/27)

4 % (1/27)

N/A

11. Best signal quality for monitoring during cardiac arrest

37 % (10/ 27)

4 % (1/27)

56 % (15/27)

4 % (1/27)

N/A

12. Change in monitoring in case of low ECG signal quality

26 % (7/27) 11 % (3/27)

37 % (10/27)

7 % (2/27)

19 % (5/27)

(N/A – not applicable)

Despite the fact that guidelines recommend using adhesive pads, the

of using manual paddles are still important barriers in guideline

survey results revealed that the use of manual paddles is still common

implementation. The Hungarian study also revealed that the major

in Europe. There were just 10/27 (37 %) countries declaring use of

obstacle for adhesive pads use which were the perceived cost-

adhesive pads in both pre- and in-hospital environment in a rate of

efficiency concerns declared in 60 % of responds, however, the

76–100 %. The use of adhesive pads was declared by 63 % of the

majority of clinicians (92 %) were aware of the benefits of adhesive

respondents. There are discrepancies in the use of adhesive pads

pads use [15].

between the countries and the location of the healthcare service (preand in-hospital areas). In countries with low adhesive pads usage, we

Many of the respondents (47 %) using the manual paddles still use

see signs of growing use of adhesive pads in the pre-hospital area,

gel or electrode pastes as a coupling medium, despite the fact it is

which may be associated with awareness of the guidelines in this group

not recommended since 2005 Guidelines release [18]. The reason for

of healthcare providers which changes the former defibrillation practice

that may be low availability of gel pads is some European countries

[11, 12, 13]. In the recently published study from Hungary only 6,5 %

indicated by the respondents.

of the interviewed senior consultants of the intensive care units and emergency departments from audited 56 hospitals declared the use of

The use of adhesive pads is the leading technique for initial cardiac

adhesive pads routinely at the time of the survey [15].

arrest rhythm assessment (56 % of respondents), however, the quick-

The 2015 Resuscitation Guidelines recognize a possibility of providing defibrillation with manual paddles in case of lack of adhesive pads [1], however, there is limited number of evidence how frequent it happens and what is the technique of defibrillation performed with manual paddles since the Guidelines do not provide any information regarding this topic. Based on previous reports on this topic we identified the most common techniques of performing defibrillation. The questionnaire contained a field for any other technique, however, no respondent suggested a different approach. In our study three different techniques of manual paddles use were reported. Two of them include charging the defibrillator during chest compression delivery. The difference between them is the location of the paddles – either on the patient’s chest (29 %) or on the defibrillator (43 %). Currently, there is no evidence to determine which technique is better in terms of chest compression quality, safety of the rescuer and pre- and post-shock pauses in chest compressions.

compressions during charging the defibrillator, which, despite the short time it takes for charging of the modern defibrillator, still generates long pauses in chest compression delivery. The survey was performed 3 months after delivery of the 2015 Guidelines, however, the 2005 technique was still reported as being used, which may reflect current practice in some European countries. There are also differences in performing defibrillation with adhesive pads (charging the defibrillator towards the end of every 2 min cycle of CPR). This is also recognized in the 2015 guidelines by the ALS writing group, however, the benefit from

of respondents declaring 3-lead ECG use for initial monitoring. The choice of the different approach to initial cardiac rhythm assessment may influence the outcome of resuscitation. One of the key changes in ERC ALS Guidelines since 2010 is keeping the focus on the use of adhesive pads and a defibrillation strategy to minimize the preshock pause [1]. The use of 3-lead ECG monitoring for initial rhythm assessment is definitely inferior to either adhesive pads or “quick look” with paddles [9], however, five of the respondents who declared adhesive pads use chose 3-lead ECG monitoring for that purpose. There are also different approaches to the technique of defibrillation attempts when shockable rhythm is present during the quick-look assessment technique. Further studies are needed to indicate the optimal approach. When a low quality signal was detected, 10/27 (37 %) of the survey respondents changed the method of monitoring to 3-lead ECG, 7/27 (26 %) looked for better signal quality with adhesive pads use and 5/27 (19 %) of respondents did not change the method of monitoring. The quality of the ECG signal is vital during cardiac arrest management and may influence therapeutic decisions. Currently, there are no human studies known to the authors of this paper assessing this issue in terms of cardiac arrest management.

Study limitations

this intervention is unknown [1, 16, 17]. The study is limited by the small number of respondents: only those Interestingly, an economic reason for not using adhesive pads,

ERC National Representatives who decided to respond to the on-

even though high 9/14 (64 %), was not the only reason indicated by

line questionnaire. We did not receive responses from all European

respondents. Resistance to using adhesive pads and the tradition

countries which may generate a bias.

RESUSCITATION TODAY - AUTUMN 2016

Five of the respondents declared they did not perform chest

look technique appears to be used at a similar level (22 %) with 19 %

EDUCATION Some respondents, however, representing their country, have found difficulties in indicating the exact percentage of adhesive pads use in their countries which hinders drawing clear conclusions. On the other hand it was the only way to collect preliminary data showing how defibrillation is performed in Europe. There were suggestions from the survey participants that the study should be open to a wider group of respondents in each country.

Conclusions Based on the observations as presented above, we conclude that there are limitations and barriers in implementation of the defibrillation technique guidelines. There are still countries where the use of adhesive pads is low due to economic and traditional reasons. There is a need for further efforts focused on guidelines implementation in terms of the use of adhesive pads and a defibrillation strategy to minimize the preshock pause.

Declarations Acknowledgements The authors wish to acknowledge their gratitude to Ruud Koster for fruitful discussions and support as well as Bart Vissers from the ERC Office for his help in acquiring data. The study was supported by Leading National Research Center 2012–2017. Figure 1 is based on a map by Maix (Wikimedia Commons, https://commons.wikimedia. org/wiki/File:Blank_map_of_Europe.svg) used with permission under Creative Commons CC-BY-SA 2.5 license. We would like to thank all respondents to the survey. The alphabetical list of the survey contributors: Souhail Alouini, Janusz Andres, Pascal Cassan, Diane Cimpoesu, Carlo Clarens, Michael Baubin, Kubilay Demirag, Zlatko Fišer, Jan-Thorsten Gräsner, Michael Colquhoun, Silvija HunyadiAnticevic, Marios Georgou, Jonathan Joslin, Jozef Köppl, Kristian Lexow, Freddy Lipert, Romano Mauri, Victor Moroz, Nicolas Mpotos, Ferenc Nagy, Federico Semeraro, Anatolij Truhlár, Jukka Vaahersalo, Felix Valsson, Elmer van den Berghaage, Dušan Vlahovic, Henrik Wagner. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate RESUSCITATION TODAY - AUTUMN 2016

if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Competing interests The authors declare that they have no competing interests.

Authors’ contributions PK conceived the idea for the study. PK, AK, JA contributed to the design of the research. PK, AK were involved in data collection. AK made descriptive statistical analysis. All authors interpreted the data, edited and approved the final version of the manuscript.

Authors’ Affiliations (1) Department of Anaesthesiology and Intensive Care, Jagiellonian University Medical College (2) Department of Bioinformatics and Telemedicine, Jagiellonian University Medical College

References 1. Soar J, Nolan JP, Böttiger BW, Perkins GD, Lott C, Carli P, et al. European Resuscitation Guidelines for Resuscitation 2015. Section 3. Adult advanced life support. Resuscitation. 2015;95:100–47.View 2. Larsen MP, Eisenberg MS, Cummins RO, Hallstrom AP. Predicting survival from out-ofhospital cardiac arrest: a graphic model. Ann Emerg Med. 1993;22(11):1652–8. 3. Valenzuela TD, Roe DJ, Cretin S, Spaite DW, Larsen MP. Estimating effectiveness of cardiac arrest interventions: a logistic regression survival model. Circulation. 1997;96(10):3308–13. 4. Edelson DP, Abella BS, Kramer-Johansen J, Wik L, Myklebust H, Barry AM, et al. Effects of compression depth and pre-shock pauses predict defibrillation failure during cardiac arrest. Resuscitation. 2006;71(2):137–45. 5. Eftestøl T, Sunde K, Steen PA. Effects of interrupting precordial compressions on the calculated probability of defibrillation success during out-of-hospital cardiac arrest. Circulation. 2002;105(19):2270–3. 6. Gundersen K, Kvaløy JT, Kramer-Johansen J, Steen PA, Eftestøl T. Development of the probability of return of spontaneous circulation in intervals without chest compressions during out-of-hospital cardiac arrest: an observational study. BMC Med. 2009;7:6. 7. Deakin CD, Nolan JP, Sunde K, Koster RW. European Resuscitation Council Guidelines for Resuscitation 2010 Section 3. Electrical therapies: automated external defibrillators, defibrillation, cardioversion and pacing. Resuscitation. 2010;81(10):1293–304. 8. Perkins GD, Davies RP, Soar J, Thickett DR. The impact of manual defibrillation technique on no-flow time during simulated cardiopulmonary resuscitation. Resuscitation. 2007;73(1):109–14. 9. Perkins GD, Roberts C, Gao F. Delays in defibrillation: influence of different monitoring techniques. Br J Anaesth. 2002;89(3):405–8.View ArticlePubMedGoogle Scholar 10. Stults KR, Brown DD, Cooley F, Kerber RE. Self-adhesive monitor/defibrillation pads improve prehospital defibrillation success. Ann Emerg Med. 1987;16(8):872–7. 11. Krawczyk P, Kononowicz AA, Andres J. Manual defibrillation technique – A pilot survey of European performance – poster presentation abstract. Resuscitation. 2012;83:e24–e123. 12. Cebula G, Koszowski P, Krawczyk P, Kononowicz AA, Odrzywołek R, Andres J. Manual defibrillation according to the 2010 European Resuscitation Council (ERC) Guidelines – is there a consensus? Report from 6th International Emergency Medicine Championship. Resuscitation. 2011;82S1:S1–S34. 13. Cebula G, Krawczyk P, Kononowicz AA, Koszowski M, Odrzywołek R, Andres J. Manual defibrillation using paddles - Which is the best technique? Resuscitation. 2012;83:e127–8. 14. The archived Defibrillation Technique Survey 2016 questionnaire: http://bioinformatics.cmuj.krakow.pl/limesurvey/index.php?sid=35971&lang=en Accessed on 9th February 2016. 15. Dioszeghy C, Molnar N. Current practice and perspective of hands-free defibrillation in Hungary – Investigating the obstacles of implementation. Interv Med Appl Sci. 2014;6(2):69–74. 16. Edelson DP, Robertson-Dick BJ, Yuen TC, Eilevstjønn J, Walsh D, Bareis CJ, et al. Safety and efficacy of defibrillator charging during ongoing chest compressions: a multi-center study. Resuscitation. 2010;81:1521–6. 17. Hansen LK, Mohammed A, Pedersen M, Folkestad L, Brodersen J, Hey T et al. The StopOnly-While-Shocking algorithm reduces hands-off time by 17 % during cardiopulmonary resuscitation - a simulation study. Eur J Emerg Med 2015. [Epub ahead of print] 18. Nolan JP, Deakin CD, Soar J, Bottiger BW, Smith G. European Resuscitation Council Guidelines for Resuscitation 2005 Section 4. Adult advanced life support. Resuscitation. 2005;67 Suppl 1:S39–86.

EVIDENCE

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EVIDENCE

OPENING THE DOOR TO RESEARCH IN A&E Accident and Emergency (A&E)

Understandably then, when the opportunity

to work by affecting the brain and spinal

Departments in hospitals are busy and

to contribute to a commercial acute pain

cord making the patient less responsive

unpredictable places where priorities can

study arose, the Emergency Department at

to excitement and pain. It comes in a

change at a moment’s notice. No wonder

Nottingham University Hospitals NHS Trust

hand-held inhaler and, in contrast to other

then that it’s a difficult environment to

(NUH) was keen to take part. But this was

methods; the inhaler is safe, effective, and

deliver research. Support provided by

the first time the Emergency Department

simple to self-administer meaning that

the Comprehensive Clinical Research

had ever worked on a commercial study

patients can control their own pain relief.

Network recently helped one Trust to

and that, combined with specific challenges

overcome the challenges of A&E and

of conducting clinical research in the

become the top recruiting site in an acute

Emergency Department environment, meant

pain study.

that this was no easy task. A constant reevaluation of priorities, and the necessity

Acute pain is the most common reason

for clinical care to take precedence over

why patients visit A&E, or the Emergency

research, makes delivering clinical studies

Department (ED) as it’s often called. It’s

in any Emergency Department extremely

also a common complaint of patients in

difficult.

family practice. Acute pain can be caused in many ways and is often a symptom

In spite of this, the Trust’s participation

of illness, childbirth, sports injuries and

was made possible with support from Trent

surgery. Yet despite substantial advances

Comprehensive Local Research Network

in pain management and research in recent

and NUH Research and Innovation working

decades, inadequate acute pain control is

collaboratively with Orion Clinical Services

still more the rule rather than the exception.

(Contract Research Organisation).

If unmanaged, experts warn that acute pain can evolve into chronic (long-term) pain

The study is testing a new pain relief

and result in extended hospital stays.

medicine called Penthrox which is thought

Making this study happen required extensive Network support including: • Good Clinical Practice (GCP) training given to staff with limited or no previous clinical research experience • Access to additional staff – a research nurse was recruited to support the study with active recruitment • Rapid confirmation of eligibility of patients • Speedy coordination of the team needed to recruit, randomise and administer the drug to avoid delays in getting pain relief to patients. This led to significant results for the team. Overall the study had a minimum target of 300 patients (adolescents aged 12-18 years) across six sites and Nottingham has proved to be the highest recruiting site to

RESUSCITATION TODAY - AUTUMN 2016

date with 62 patients (with an initial target of 60) a clear cut above the other five sites. Paul Curtis, Project Manager at Orion Clinical Services reflects on the team’s success so far: “Nottingham have been our flagship site. The team have really demonstrated how to successfully conduct a clinical trial in a difficult ED environment. Their collective effort and commitment to overcome studyResearch reality. Clinical trials can be hard to conduct in an Emergency Department setting

related issues has provided the backbone to our overall study recruitment.”

EVIDENCE Key points/impacts • The Network used a number of tools at its disposal to underpin the Trusts research capacity and capability to contribute to this study • As a result, the site demonstrated was selected to contribute to this commercial study • Ongoing network support provided an efficient and targeted approach to study recruitment • The site exceeded it’s recruitment target and became the top recruiting site to date • Increased research capability and capacity has placed the site in a strong position to deliver further collaborative commercial research. As a result of involvement with this study

from Research and Innovation and the

Such a unit will no doubt be strengthened

the research capacity and capability

Comprehensive Local Research Network,

by a successful commercial research

within the Emergency Department at the Trust has now significantly grown. There are now three full-time research nurses in

I am part of a team developing a ‘Front Door’ research unit in Nottingham which

portfolio, which this study has started.” More info about this article:

post, a GCP trained Emergency Medical

will work closely with other NHS Trusts in

emma.wragg@nihr.ac.uk

Practitioner and eight GCP trained doctors.

the region and with the ambulance service.

www.crncc.nihr.ac.uk/about_us/ccrn

Furthermore, Frank Coffey, the Co-Specialty Group lead for Injuries and Emergencies and chief investigator for the study, is keen to increase collaborative research studies like these across the region: “With colleagues from Acute Medicine

Team effort. Emergency Department units are strengthened by successful commercial research

“Their collective effort and commitment to overcome studyrelated issues has provided the backbone to our overall study recruitment”

RESUSCITATION TODAY - AUTUMN 2016

“Such a unit will no doubt be strengthened by a successful commercial research portfolio, which this study has started”

and the Trauma Network, and support

EVIDENCE

CAPILLARY LACTATE CONCENTRATION ON ADMISSION OF NORMOTENSIVE TRAUMA PATIENTS: A PROSPECTIVE STUDY Pierre Bouzat1, 2, 3, Clotilde Schilte1, 2, Marc Vinclair1, Pauline Manhes1, Julien Brun1, Jean-Luc Bosson4 and JeanFrançois Payen1, 2, 3 Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine201624:82 DOI: 10.1186/s13049-016-0272-x ©The Author(s). 2016

Abstract

Trial registration

Background

ClinicalTrials.gov, No. NCT01793428.

Elevated serum blood lactate is an indicator of on-going bleeding

Keywords

in severe trauma patients. Point-of-care (POC) capillary lactate measurement devices may be useful to rapidly assess lactate concentration at the bedside. The aim of this study was to test the

Lactate, Point-of-care, Transfusion, Severe trauma

diagnostic performance of capillary lactate to predict significant transfusion in normotensive trauma patients.

Methods We conducted a prospective observational study in one level-I trauma centre. From August 2011 to February 2013, 120 consecutive adult patients with systolic blood pressure (SBP) higher than 90 mmHg were included. Capillary lactate was measured on admission in the trauma bay. The primary outcome was defined as a significant transfusion within the first 48 h. Diagnostic performance was determined using receiver operating characteristic (ROC) curve analysis. We also tested the agreement between capillary lactate and blood lactate concentrations using Bland and Altman analysis.

Results Of the 120 normotensive trauma patients, 30 (25 %) required at least one unit of packed red blood cells (RBC) and 12 (10 %) patients received at least four RBC within the first 48 h. All patients with significant RBC RESUSCITATION TODAY - AUTUMN 2016

transfusion had capillary lactate higher than 3.5 mmol/l. The area under the ROC curve of capillary lactate on admission to predict transfusion of at least 4 RBC units was 0.68 [95 % CI 0.58 – 0.78]. The average bias between capillary and blood lactate measurements was 2.4 mmol/l with a standard deviation of 3.0 mmol/l (n = 60 patients).

Background Increase in lactate concentration is a common indicator of severity in critically ill patients [1, 2, 3]. After severe trauma, elevated serum lactate concentration was also associated with short-term outcomes. In preclinical studies, arterial lactate concentration was a strong predictor of blood loss after blunt or penetrating trauma [4, 5, 6]. In the clinical setting, initial lactate measurement was associated with organ failure and mortality in 129 trauma patients [7]. Blood lactate concentration was also an independent variable associated with mortality in 586 trauma patients [8]. Taken together, these studies highlight the role of arterial lactate concentration to screen high-risk patients for transfusion in the trauma bay. Other classic vital parameters like heart rate or systolic arterial blood pressure (SBP) are common markers to predict critical bleeding in severe trauma patients [9]. Therefore, the additional information brought by serial lactate measurements may be obscured by classic physiological parameters in shocked patients. Interestingly, the yield of lactate concentration in a selected population of trauma patients with SBP between 90 and 110 mmHg allowed for early identification of patients requiring significant transfusion [10]. In patients with normal vital signs, elevated arterial lactate concentration was also found to be associated with occult major trauma [11]. These results were further corroborated in normotensive elderly blunt trauma patients [12]. Therefore, the additional benefit of arterial lactate concentration

Conclusions

to detect patients at risk for transfusion may be superior in patients with normal vital signs compared to patients with shock on admission. However, measuring arterial lactate requires an automatic blood gas

Although a significant association was found between POC lactate

test and arterial blood sampling, which could be seen as invasive

concentration and transfusion requirements, the diagnostic performance

and expensive in patients with normal vital signs. To overcome these

of capillary lactate measurements was poor. Due to large disagreement

limitations, handheld point-of-care (POC) fingertip lactate measurement

between capillary lactate and blood lactate, capillary lactate cannot be

was implemented in emergency departments with adequate accuracy to

considered in the clinical setting.

determine moderate increase in lactate levels [13].

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EVIDENCE Using this device in the pre-hospital setting, capillary lactate concentration

injury, vital parameters (heart rate, SBP) in the pre-hospital field, pre-

higher than 3.5 mmol/l was associated with in-hospital mortality in a study

hospital shock index defined as the ratio between heart rate and SBP,

of 124 severe trauma patients requiring urgent ambulance dispatching [14].

total volume of infusion (colloid and crystalloids), number of RBC units transfused within the first 48 h, emergency treatment for haemostasis

The aim of the present study is to assess whether capillary lactate on

(embolization and/or damage control surgery including laparotomy,

admission can predict transfusion in trauma patients with a SBP higher

thoracotomy and orthopaedic surgery for haemostasis), length of stay

than 90 mmHg. We also test the ability of the pre-hospital shock index

in intensive care unit (ICU), injury severity score (ISS), and in-hospital

defined as the ratio between heart rate and SBP to predict a significant

mortality. Biological data consisted of capillary lactate and capillary

transfusion. We assume that capillary lactate higher than 3.5 mmol/l can

haemoglobin. Serum blood lactate was also collected if available.

predict significant transfusion within the first 48 h post-trauma, with a higher accuracy than the pre-hospital shock index.

Endpoints The primary outcome was a significant transfusion within the first posttraumatic 48 h defined by a transfusion of at least six RBC units.

Methods Study design and patients We conducted a prospective observational study. Consecutive trauma patients with SBP higher than 90 mmHg were included from August 2011 to February 2013 in one level-I trauma centre (Grenoble University Hospital, Grenoble, France). The Regional Institutional Ethics Committee (Comité d’Ethique des Centres d’Investigation Clinique de l’inter-région Rhône-Alpes-Auvergne, IRB number 5708) approved the study design and, given its observational nature, waived the requirements for written informed consent from each patient. This study is registered with

The secondary outcomes were: 1) blood lactate concentration to determine the agreement with the POC capillary lactate measurement; 2) a significant transfusion defined by at least four RBC units within the first 48 h; 3) the allocation of transfusion according to abnormal (≥3.5 mmol/l) or normal (< 3.5 mmol/l) capillary lactate concentration on admission. Study size To be clinically relevant, we expected 90 % sensitivity for capillary lactate to predict a significant transfusion. The number of patients to be included was set at 120 patients to obtain an acceptable 95 %

ClinicalTrials.gov No. NCT01793428.

confidence interval (95 % CI) between 83 and 95 %.

Inclusion criteria were patients older than 18 year-old, admitted in

Statistical analysis

the trauma bay for suspected severe trauma with a SBP higher than 90 mmHg. Severe trauma was suspected in the pre-hospital setting using the French Vittel triage criteria [15]. Exclusion criteria included pregnancy, chronic liver disease, pre-hospital transfusion, pre-hospital infusion of norepinephrine higher than 0.1 mcg/kg/min and body core

Descriptive statistics included frequencies and percentages for categorical variables, and median values (25th–75th percentiles) for continuous variables. The diagnosic performance of capillary lactate to predict transfusion was evaluated using the area under of the receiver operating characteristic curve (AUC-ROC) with its 95 % confidence interval (95 %

temperature lower than 35 °C.

CI). Sensitivity and specificity were also calculated at the threshold that

Capillary lactate measurement

lactate and the serum lactate concentration was done using a Bland &

The handheld POC capillary lactate measurement device used in this study was the lactate scout® (Senslab, Leipzig, Germany). The lactate analyser is a small device with dimensions of 9.1 × 5.5 × 2.4 cm and weighing 85 g, including batteries. Reactive strips are used for the analysis of lactate using an enzymatic-amperometric biosensor as the measuring element. The measurement range goes from 0.5 to 25.0

privileges sensitivity [17]. The agreement between the POC capillary Altman representation [18]. Since only one measurement by each method was taken on each person, and the difference across the range was not constant, we decided to regress the differences on the averages and use the resulting equation to construct limits of agreement [19]. Comparisons between patients with capillary lactate higher or equal to 3.5 mmol/L and those with normal capillary lactate (< 3.5 mmol/l) were done using a chi-

RESUSCITATION TODAY - AUTUMN 2016

mmol/l, and only 0.2 μl of blood is required for the analytical process.

square test for categorical variables and using the Mann-Whitney non

Study protocol and data collection

with R software (version 3.1.2, https://cran.r-project.org). A p value of 0.05

Patients were included at hospital admission, immediately after the

parametric test for continuous variables. Statistical analysis was performed or less was considered statistically significant.

pre-hospital phase. Two consecutive capillary lactate measurements were performed on admission concomitantly to capillary haemoglobin and glucose assessment. These measurements were performed by

Results

the nurse in charge of the patient using the same puncture. Sites of capillary puncture were located at fingertip or ear lobe. The average

We included 120 consecutive patients within the study period.

concentration of capillary lactate was recorded for analysis. Arterial or

Characteristics of the trauma population are summarized in Table 1.

venous blood lactate concentration was concomitantly assessed when

The typical patient was a young, male adult admitted for blunt trauma.

serum lactate concentration was prescribed by the attending physician.

Trauma severity in our cohort was moderate (median ISS = 19) and only

Arterial and venous lactate values were pooled since no discrepancy

two patients out of 120 (2 %) did not survive. Median concentrations of

between these two variables was found in sepsis [16]. Physicians in

capillary and serum lactate are presented in Table 1. Thirty-two (27 %)

charge of the patient were not informed about capillary lactate values.

patients required emergency treatment for haemostasis (embolization or damage control surgery). Seventy-five (63 %) patients were directed to

The following clinical data was collected: age, gender, mechanism of

the ICU after their admission into the trauma bay.

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EVIDENCE Thirty (25 %) patients received at least one unit of RBC within the first 48 h. Only four (3 %) patients received a transfusion of at least six RBC units. The low incidence of the primary outcome did not allow us to explore the diagnostic performance of capillary lactate to predict transfusion of at least six RBC. Nevertheless, twelve (10 %) patients had at least four RBC units within the first 48 h (secondary outcome).

Table 1 Characteristics of the global population (n = 120 patients) Variable

Value

Age, years

37 [27–56]

Male, n (%)

102 (85 %)

Blunt, n (%)

113 (94 %)

Prehospital SBP, mmHg

116 [100–131]

Prehospital HR, beats/min

80 [71–94]

Prehospital Shock index, n (%): < 0.9

81 (76 %)

> 0.9

26 (24 %)

Prehospital Crystalloids, ml

250 [0–500]

Prehospital Colloids, ml

0 [0–0]

Capillary lactate

3.7 [2.3–5.6]

Blood lactate*

1.6 [1.1–2.7]

Capillary hemoglobin, g/dl

13.6 [12.5–14.9]

Emergency surgery, n (%)

28 (23 %)

Embolization, n (%)

4 (3 %)

ISS

19 [10–26]

Length of stay in ICU, n (%)

7 [3–14]

Intra-hospital mortality, n (%)

2 (2 %)

Transfusion ≥ 4 RBC within 48 h, n (%)

12 (10 %)

Values are median [25th–75th percentiles] RBC packed red Blood Cell; SBP systolic blood pressure, HR heart rate, ICU intensive care unit, ISS injury severity score *n = 60 patients

RESUSCITATION TODAY - AUTUMN 2016

The AUC-ROC of capillary lactate on admission to predict significant transfusion was 0.68 [95 % CI 0.58 – 0.78] (see Fig. 1 and Additional file 1). Maximizing the sensitivity, we found a threshold at 3.5 mmol/l. Sensitivity at this cut-off was 100 % (95 % CI 74–100 %) and specificity was 53 % (95 % CI 43–62 %). The AUC-ROC of the shock index was similar: 0.68 [95 % CI 0.51 – 0.85] (see Fig. 1 and Additional file 1). The AUC-ROC of capillary lactate on admission to predict any transfusion was only 0.59 [95 % CI 0.46 – 0.72] whereas the AUC-ROC of serum lactate was 0.77 [95 % CI 0.62 – 0.91]. Agreement between capillary lactate and serum blood lactate was performed in 60 patients. Bland & Altman analysis is presented in Fig. 2. Average bias between the two methods was 2.4 mmol/l with a standard deviation of 3.0 mmol/l. The capillary lactate minus blood lactate difference was positively correlated with the capillary and blood lactate average (capillary – blood lactate = -1.6 + 1.26 × (capillary + blood lactate)/2, p < 0.001), indicating larger discrepancy between the two measurements in patients with abnormal lactate concentration. We used this linear bias to assess the 95 % prediction limits for the blood lactate given the value by the capillary method (Fig. 2). Univariate analyses between the group of patients with capillary lactate ≥ 3.5 mmol/l (n = 62 patients) and the group of patients with capillary lactate < 3.5 mmol/l (n = 58 patients) is shown on Table 2. Patients in the abnormal capillary lactate group had lower capillary haemoglobin, higher prehospital heart rate and more emergency haemostatic treatment than the normal capillary lactate group. The allocation of transfusion in the two groups is presented in Fig. 3. All patients receiving at least four RBC units had capillary lactate higher than 3.5 mmol/L.

>>>

Fig. 1 Receiver operating characteristic curves of capillary lactate on admission and prehospital shock index to predict a significant transfusion in the cohort (n = 120 patients)

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EVIDENCE

Table 2 Univariate analysis between patients with capillary lactate < 3.5 mmol/l (n = 58 patients) versus patients with capillary lactate ≥ 3.5 mmol/l (n = 62 patients) Capillary lactate <3.5 mmol/l

Capillary lactate ≥3.5 mmol/l

N = 58 patients

N = 62 patients

Age, years

34.7 [26.3–55.1]

38 [28.2–56.5]

0.61

Male, n (%)

50 (86 %)

52 (84 %)

0.72

Blunt trauma, n (%)

51 (88 %)

60 (97 %)

0.47

Prehospital SBP, mmHg

120 [100–136]

111 [100–129]

Prehospital HR, beats/min

77 [69–86]

82 [75–100]

0.26

< 0.9

42 (72 %)

42 (68 %)

0.01

> 0.9

16 (28 %)

20 (32 %)

Prehospital Shock index, n (%) :

p-value

0.9

Prehospital Crystalloid, ml 250 [0–500] 250 [0–500] Fig. 2 Agreement between the capillary lactate measurement device and serum blood lactate concentration via the Bland & Altman Prehospital Colloid, ml 0 [0–0] 0 [0–0] representation (n = 60 patients). Central dash-line represents the linear bias between the two methods. Upper and lower black lines represent the Capillary lactate limits for the blood lactate given the 2.2 value [1.4–2.6] 5.6 [4.5–7.2] <0.001 95 % prediction by the capillary method Blood lactate*

1.45 [1–1.9]

Capillary haemoglobin, g/dl

13.9 [13.0–15.0]

Emergency surgery, n (%) Discussion

10 (17.2 %)

Embolization, n (%) 0/58 (0 %) In a selected cohort of trauma normotensive patients, we found a poor ISS 19 [10–26]

diagnostic performance of capillary lactate to predict the transfusion of at least Length of stay in ICU, n (%) 7 [3–19] 4 RBC units. More concerning was the poor agreement between the capillary In-hospital mortality, n (%) 1 (2 %) method and the serum blood lactate concentration. Although significant Transfusion ≥4 RBC first 48 h, n (%) 0 (0 %) association was found between capillary lactate and transfusion requirements,

2.1 [1.4–3.2]

<0.01

13.1 [11.7–14.5] 0.02 had more embolization procedures than patients with normal capillary 18 (29 %) 0.13

lactate. Accordingly, transfusion needs were also higher in the capillary 4/62 (6.5 %) 0.04 lactate ≥ 3.5 mmol/l group and all significantly transfused patients were 18 [10–26] 0.9 part of this group. These findings were in line with prehospital evaluation 6.5 [3.3–12.8] <0.01 of POC fingertip lactate device, where pre-hospital blood lactate levels (2 %) 0.58 were associated with1in-hospital mortality [14]. In this study, capillary 12by (19nurses %) 0.96 lactate was performed from the emergency medical service

Values are median [25th–75th percentiles] and provided more prognostic information than vital signs alone. the lack of accuracy of capillary lactate weakens the use of this POC device at RBC packed Red Blood Cell, SBP systolic blood pressure, HR heart rate, ICU intensive care unit, ISS injury severity score. P value < 0.05 are indicated in bold In our study, we confirmed that capillary lactate could be achieved the bedside to detect occult trauma in non-shocked trauma patients. *n = 60 patients

by the nurse in charge of the patient. However, we found statistical

RESUSCITATION TODAY - AUTUMN 2016

Capillary lactate higher than 3.5 mmol/l was statistically associated with

association but failed to demonstrate sufficient accuracy to predict

transfusion requirements in our cohort. Indeed, this group of patients

transfusion needs. Indeed, the AUC-ROC was low with a lower limit of

Fig. 3 Allocation of packed red blood cells (RBC) units across individual patients according to the category of capillary lactate concentration on admission (< 3.5 mmol/l vs. ≥ 3.5 mmol/l). The dash-line represents the cut-off for significant transfusion (four RBCs). * p < 0.01

EVIDENCE Table 2 Univariate analysis between patients with capillary lactate < 3.5 mmol/l (n = 58 patients) versus patients with capillary lactate ≥ 3.5 mmol/l (n = 62 patients) Capillary lactate <3.5 mmol/l

Capillary lactate ≥3.5 mmol/l

N = 58 patients

N = 62 patients

Age, years

34.7 [26.3–55.1]

38 [28.2–56.5]

0.61

Male, n (%)

50 (86 %)

52 (84 %)

0.72

Blunt trauma, n (%)

51 (88 %)

60 (97 %)

0.47

Prehospital SBP, mmHg

120 [100–136]

111 [100–129]

Prehospital HR, beats/min

77 [69–86]

82 [75–100]

0.26

< 0.9

42 (72 %)

42 (68 %)

0.01

> 0.9

16 (28 %)

20 (32 %)

250 [0–500]

p-value

Prehospital Shock index, n (%) :

Prehospital Crystalloid, ml

0.9

Prehospital Colloid, ml

0 [0–0]

Capillary lactate

2.2 [1.4–2.6]

5.6 [4.5–7.2]

<0.001 <0.01

Blood lactate*

1.45 [1–1.9]

2.1 [1.4–3.2]

Capillary haemoglobin, g/dl

13.9 [13.0–15.0]

13.1 [11.7–14.5]

Emergency surgery, n (%)

10 (17.2 %)

18 (29 %)

0.13

Embolization, n (%)

0/58 (0 %)

4/62 (6.5 %)

0.04

0.02

ISS

19 [10–26]

18 [10–26]

Length of stay in ICU, n (%)

7 [3–19]

6.5 [3.3–12.8]

0.9

In-hospital mortality, n (%)

1 (2 %)

0.58

Transfusion ≥4 RBC first 48 h, n (%)

0 (0 %)

12 (19 %)

0.96

<0.01

Values are median [25th–75th percentiles] RBC packed Red Blood Cell, SBP systolic blood pressure, HR heart rate, ICU intensive care unit, ISS injury severity score. P value < 0.05 are indicated in bold *n = 60 patients

its 95 % confidence interval close to 0.5. This result clearly affected the

be interferences between capillary lactate assessment and interstitial

diagnostic performance of capillary lactate at the early phase of severe

oedema due to fluid overloading [23]. However, total infused volume

trauma. In a larger retrospective cohort, blood lactate had larger AUC

was low in our study according to the moderate severity of the patients.

to predict significant transfusion at hospital admission (0.76) but no 95 % confidence interval was provided [10] and lactate was measured on

We acknowledge several limitations of our study. First, the incidence

blood samples. Interestingly, the same group found that prehospital

of the primary outcome was too low to explore capillary lactate

shock index might facilitate the early identification of patients at risk

in patients that received at least six RBC units. Nevertheless, the

for massive transfusion [20]. In our cohort of patients receiving less

incidence of four RBC transfusions was relatively high in our cohort

transfusion, we reported similar diagnostic performance for serum lactate

(10 %). Moreover, a transfusion of four RBC units may be considered

(AUC ROC = 0.77 to predict any transfusion) but we did not report good diagnostic performance of prehospital shock index with an AUC-ROC equal to 0.68 [95 % CI 0.51 – 0.85]. Taken together, these findings normotensive patients. Unfortunately, in our study, neither capillary lactate nor shock index had sufficient diagnostic performance to be considered pertinent in determining patients’ severity at hospital admission. The poor predictive value of capillary lactate might be related to the poor agreement between this method and the serum blood lactate measurement since average bias between the two methods was 2.4

a total volume of one litre. Second, the sample size of the cohort is relatively small and the limited number of events should be considered when interpreting our results. However the lack of agreement between the POC fingertip device and the reference method is valuable and questions the relevancy of capillary lactate measurement device in daily practice. Third, standardized capillary lactate measurement were not performed by one dedicated nurse. Nevertheless, this study was meant to be pragmatic and POC devices should be practical enough to be generalized in the trauma bay independently of the executing nurse.

mmol/l. Considering normal lactate range from 0 to 3.5 mmol/l, such Fig. 3the Allocation of packed blood One cells explanation (RBC) units across individual patients according to the category of capillary lactate concentration on bias limits usefulness of POCred device. for this (< 3.5 mmol/l contamination vs. ≥ 3.5 mmol/l). dash-line represents the cut-off for significant transfusion (four RBCs). * p < 0.01 result admission may be extra-capillary by The sweat composition [21].

Conclusions

Under intense physical exercise, lactate could be measured on the skin surface and may overestimate capillary lactate value. As severe trauma

Capillary lactate was associated with transfusion requirements in

often occurs during sport-related accident in our region [22], this type of

normotensive trauma patients. However, we did not find sufficient

contamination may be expected in our patients. Other explanation may

accuracy of this technique for transfusion prediction at the bedside.

RESUSCITATION TODAY - AUTUMN 2016

illustrate the need for reliable information to detect occult severe trauma in

significant from the clinical standpoint since this quantity represents

EVIDENCE The poor agreement between this device and the standard method may hinder the usefulness of capillary lactate in daily clinical practice. Despite encouraging statistical associations, capillary lactate may not add relevant information about occult severe bleeding in non-shocked trauma patients.

Declarations Acknowledgements The authors thank Senan Doyle, PhD for English correction and Céline Genty, MSc for specific statistical analysis. Authors’ contributions PB, PM, CS, MV, JLB and JFP conceived the study and designed the trial. PB, CS, PM, JB and MV supervised the conduct of the trial and data collection. PB, CS, MV, JB and JFP undertook recruitment of the patients and managed the data. JLB, PB and JFP provided statistical advice on study design and analyzed the data. PB, CS, PM and JFP drafted the manuscript, and all authors contributed substantially to its revision. PB takes responsibility for the paper as a whole. All authors read and approved the final manuscript. Competing interests The author declares that they have no competing interests. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Additional file Additional file 1: Detailed data of the receiver operating characteristic curves for capillary lactate and shock index to predict significant tranfusion. (DOCX 25 kb)

Authors’ Affiliations (1) Pôle Anesthesie Reanimation, CHU Grenoble Alpes RESUSCITATION TODAY - AUTUMN 2016

(2) University Grenoble Alpes (3) INSERM U1216

4. Choi JY, Lee WH, Yoo TK, Park I, Kim DW. A new severity predicting index for hemorrhagic shock using lactate concentration and peripheral perfusion in a rat model. Shock. 2012;38:635–41. 5. Moomey Jr CB, Melton SM, Croce MA, Fabian TC, Proctor KG. Prognostic value of blood lactate, base deficit, and oxygen-derived variables in an LD50 model of penetrating trauma. Crit Care Med. 1999;27:154–61. 6. Rixen D, Raum M, Holzgraefe B, Sauerland S, Nagelschmidt M, Neugebauer EA, et al. A pig hemorrhagic shock model: oxygen debt and metabolic acidemia as indicators of severity. Shock. 2001;16:239–44. 7. Manikis P, Jankowski S, Zhang H, Kahn RJ, Vincent JL. Correlation of serial blood lactate levels to organ failure and mortality after trauma. Am J Emerg Med. 1995;13:619–22. 8. Regnier MA, Raux M, Le Manach Y, Asencio Y, Gaillard J, Devilliers C, et al. Prognostic significance of blood lactate and lactate clearance in trauma patients. Anesthesiology. 2012;117:1276–88. 9. Olaussen A, Blackburn T, Mitra B, Fitzgerald M. Review article: shock index for prediction of critical bleeding post-trauma: a systematic review. Emerg Med Australas. 2014;26:223–8. 10. Vandromme MJ, Griffin RL, Weinberg JA, Rue 3rd LW, Kerby JD. Lactate is a better predictor than systolic blood pressure for determining blood requirement and mortality: could prehospital measures improve trauma triage? J Am Coll Surg. 2010;210:861–7. 7-9. 11. Paladino L, Sinert R, Wallace D, Anderson T, Yadav K, Zehtabchi S. The utility of base deficit and arterial lactate in differentiating major from minor injury in trauma patients with normal vital signs. Resuscitation. 2008;77:363–8. 12. Callaway DW, Shapiro NI, Donnino MW, Baker C, Rosen CL. Serum lactate and base deficit as predictors of mortality in normotensive elderly blunt trauma patients. J Trauma. 2009;66:1040–4. 13. Gaieski DF, Drumheller BC, Goyal M, Fuchs BD, Shofer FS, Zogby K. Accuracy of Handheld Point-of-Care Fingertip Lactate Measurement in the Emergency Department. West J Emerg Med. 2013;14:58–62. 14. Jansen TC, van Bommel J, Mulder PG, Rommes JH, Schieveld SJ, Bakker J. The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study. Crit Care. 2008;12:R160. 15. Babaud J, Ridereau-Zins C, Bouhours G, Lebigot J, Le Gall R, Bertrais S, et al. Benefit of the Vittel criteria to determine the need for whole body scanning in a severe trauma patient. Diagn Interv Imaging. 2012;93:371–9. 16. Browning R, Datta D, Gray AJ, Graham C. Peripheral venous and arterial lactate agreement in septic patients in the emergency department: a pilot study. Eur J Emerg Med. 2014;21:139–41. 17. Ray P, Le Manach Y, Riou B, Houle TT. Statistical evaluation of a biomarker. Anesthesiology. 2010;112:1023–40. 18. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307–10.

(4) Centre d’investigation clinique, CHU Grenoble Alpes

19. Carstensen B. Comparing methods of measurement: Extending the LoA by regression. Stat Med. 2010;29:401–10.

References

20. Vandromme MJ, Griffin RL, Kerby JD, McGwin Jr G, Rue 3rd LW, Weinberg JA. Identifying risk for massive transfusion in the relatively normotensive patient: utility of the prehospital shock index. J Trauma. 2011;70:384–8. discussion 8–90.

1. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care. 2014;18:503.

21. Patterson MJ, Galloway SD, Nimmo MA. Variations in regional sweat composition in normal human males. Exp Physiol. 2000;85:869–75.

2. Leone M, Bechis C, Baumstarck K, Ouattara A, Collange O, Augustin P, et al. Outcome of acute mesenteric ischemia in the intensive care unit: a retrospective, multicenter study of 780 cases. Intensive Care Med. 2015;41:667–76.

22. Bouzat P, Ageron FX, Brun J, Levrat A, Berthet M, Rancurel E, et al. A regional trauma system to optimize the pre-hospital triage of trauma patients. Crit Care. 2015;19:111.

3. Davies AR, Bellomo R, Raman JS, Gutteridge GA, Buxton BF. High lactate predicts the failure of intraaortic balloon pumping after cardiac surgery. Ann Thorac Surg. 2001;71:1415–20.

23. Ferasin L, Nguyenba TP. Comparison of canine capillary and jugular venous blood lactate concentrations determined by use of an enzymatic-amperometric bedside system. Am J Vet Res. 2008;69:208–11.

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EVIDENCE

GOOD NEUROLOGICAL OUTCOME DESPITE VERY LOW REGIONAL CEREBRAL OXYGEN SATURATION DURING RESUSCITATION - A PROSPECTIVE PRECLINICAL TRIAL IN 29 PATIENTS Christian Storm†, Alexander Wutzler†, Lars Trenkmann, Alexander Krannich, Sabrina von Rheinbarben, Fridolin Luckenbach, Jens Nee, Natalie Otto, Tim Schroeder and Christoph Leithner †Contributed equally Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 201624:43 DOI: 10.1186/s13049-016-0234-3 © Storm et al. 2016

Abstract

Keywords

Background

Cardiac arrest, Outcome, Near infrared spectroscopy, Out-of-hospital cardiac arrest

Noninvasive regional cerebral oxygen saturation (rSO2) measurement using near-infrared spectroscopy (NIRS) might inform on extent and duration of cerebral hypoxia during cardiopulmonary resuscitation

Background

(CPR). This information may be used to guide resuscitation efforts and may carry relevant early prognostic information.

The extent of hypoxic encephalopathy (HE) largely determines outcome in patients after cardiac arrest and resuscitation. In principle, the severity and duration of brain hypoxia during cardiac arrest

Methods We prospectively investigated non-traumatic out-of-hospital cardiac arrest (OHCA) patients on scene. NIRS was started either during CPR or shortly after (<2 min) return of spontaneous circulation (ROSC) by emergency medical service (EMS). Outcome was determined at intensive care unit (ICU) discharge and 6 months after cardiac arrest.

(CA) can be determined by noninvasive near-infrared spectroscopy (NIRS) during resuscitation. The brain extracts only around one third of the oxygen delivered under physiological conditions, thus normal values of frontal brain rSO2 determined by NIRS monitors are around 60–80 %. As the brain has no oxygen reserves and demand is high, brain oxygen saturation drops to very low values very shortly after cardiac arrest [1]. During total oxygen depletion, nonoxidative metabolism can deliver sufficient ATP to prevent irreversible neuronal damage for a few minutes. Hypoxic encephalopathy can only be

Results A total of 29 OHCA patients were included. In 23 patients NIRS was started during CPR and in 6 patients immediately after ROSC. 18 (62.1 %) patients did not reach ROSC. Initial rSO2 during CPR was very low (<50 % in all 23 patients, < 30 % in 19 of 23 patients) with no significant difference between patients achieving ROSC and those who did not. Of five patients with ROSC, in whom NIRS was recorded during CPR, two RESUSCITATION TODAY - AUTUMN 2016

reached a good six-months outcome (initial rSO2 22 %) and three died during the ICU stay (initial rSO2 15, 16 and 46 %). In six patients with NIRS started immediately after ROSC (<2 min), rSO2 was substantially higher (54–85 %) than in patients during CPR (p = 0.006).

prevented by restoring oxygen delivery via effective resuscitation before irreversible damage has occured. NIRS may be used to guide resuscitation efforts by indicating the achieved cerebral oxygenation which is one of the primary targets of CPR [1, 2]. Few studies have measured regional brain oxygen saturation using NIRS in patients during resuscitation [3]. The study settings were heterogeneous. Most importantly, large studies have been reported on NIRS started upon hospital arrival as opposed to studies which measured NIRS during CPR on scene [4, 5, 6, 7, 8]. Likely, measurements started during CPR upon hospital arrvial cover a much later time point after cardiac arrest as compared to measurements started during CPR on scene and thus, results obtained in these two different settings need to be compared with great care. In principle, a lower threshold for the initial rSO2 during resusciation may exist below which ROSC

Discussion and conclusion

or survival with good outcome are rare [8]. On the other hand, brain rSO2 may change rapidly during CPR and full recovery of brain tissue is possible if the periods of severe hypoxia are short enough to allow

Initial frontal brain rSO2 determined by NIRS during CPR was generally

for survival of neurons via non-oxidative metabolism [9]. To contribute

very low and recovered rapidly after ROSC. Very low initial rSO2 during

to the understanding of prognostic implications of brain oxygen

CPR was compatible with good neurological outcome in our limited

saturation during CPR, we performed a prospective study on out-

cohort of patients. Further studies are needed to assess in larger

of-hospital cardiac arrest patients using near-infrared spectroscopy

cohorts and more detail the implications of very low initial rSO2 during

to determine frontal brain rSO2 during CPR in the field at the earliest

CPR on scene.

possible time point.

EVIDENCE Methods The local ethics committee of the Charité-Universitätsmedizin Berlin

assessed, we defined good outcome as CPC 1–2 and poor outcome

approved the study protocol and the trial was registered (www.

as CPC 3–5. For the 6-months follow up, the patient or a proxy was

clinicaltrials.gov: NCT 01531426). For all survivors a healthcare proxy

contacted by telephone to assess CPC. Data on mortality was obtained

was contacted to give written informed consent as all cardiac arrest

by the German residents registry.

survivors were unconscious on admission. Nontraumatic cardiac arrest patients of cardiac and non-cardiac etiology were enrolled between January 2012 and January 2013.

Pre-hospital treatment

Statistics Statistical analysis was performed using SPSS (IBM SPSS Version 20) and R (R 3.1.2, The R Project). Due to the low number of patients, data are presented as individual values and as median and quartiles (IQR)

Advanced cardiac life support (ACLS) was performed according to

or absolute numbers and percent. For comparison of rSO2 between

current guidelines.

different groups a Wilcoxon-Mann–Whitney-Test was performed. A significance level of α = 0.05 was used.

NIRS monitoring started out-of-hospital and was continued until the end of the rewarming procedure (approximately 41 h in total) in all survivors. The INVOS monitor (INVOS 5100 C; Covidien; Mansfield, USA) was used. Of note, the lower rSO2 detection limit of the monitor was 15 % in our study. The two surface sensors were placed on the forehead for detection of bilateral frontal cerebral oxygen saturation. The monitor detects the absorption of light at wavelengths of 724 nm and 810 nm and calculates regional hemoglobin oxygen saturation (rSO2). For analysis of the recorded spectroscopy data the software package provided by COVIDIEN was used (INVOS Analytics Tool, Version 1.2). The mean value between right and left sensor was calculated. For the purposes of our preclinical study, we determined the first reliably measured value and refer to it as ‘initial rSO2’. We have previously reported rSO2

Results In 29 patients data recorded by the EMS during CPR (n = 23) or shortly after ROSC (n = 6) were available (study flow chart, Fig. 1). Baseline characteristics of all patients are given in Table 1. 18 patients (62 %) did not achieve ROSC. 11 patients (38 %) were admitted to the ICU after ROSC. Of those, three had good outcome (CPC 1–2) at ICU discharge and eight had poor outocme (one CPC 3, seven CPC 5) (Table 2). All patients discharged (n = 4) were followed up at 6 months. The three patients discharged with CPC 1–2 continued with a good neurological status (all CPC 1), one patient was discharged with CPC 3 and had died at 6 month follow up.

measurements continued until the end of hypothermia treatment [10]. An additional paramedic not involved in patient care performed the trial-related monitoring, carefully avoiding any interference with the ACLS team. The NIRS sensors were placed during cardiopulmonary resuscitation or within two minutes after ROSC. Forehead and upper part of the body positioning was standardized at 30° in all patients during the whole period of treatment and this position was adopted immediately after ROSC at the scene.

Hospital treatment local standard operating procedure and post-resuscitation care according to current guidelines as described in detail elswhere (24 h at 33 °C followed by slow rewarming 0.25°/h) [10]. Hypothermia was performed with a computer controlled feedback surface-cooling device (Arctic Sun; C.R.BARD).

Outcome assessment For survivors, outcome was assessed at discharge from the ICU and at 6-months follow up by the Pittsburgh Cerebral Performance Category

Fig. 1 Flow chart of the trial population. CPR cardiopulmonary resuscitation; ROSC return of spontaneous circulation; *NIRS starteted after ROSC within ≤ 2 min; CPC cerebral performance category (1–2 good neurological outcome; CPC 3–5 poor neurological outcome); CA cardiac arrest

RESUSCITATION TODAY - AUTUMN 2016

All patients received cardiac arrest treatment according to our written

(CPC) Scale. Because both short and long-term outcomes were

EVIDENCE Initial regional oxygen saturation and ROSC

Withdrawal of treatment

Of 23 patients with NIRS started during CPR,18 never reached ROSC. Clinical details and initial rSO2 of the individual patients are shown in Table 2. Figure 2 illustrates initial rSO2 of patients who did not achieve ROSC (‘no ROSC’), those in whom NIRS was started during CPR and who achieved ROSC (‘pre-ROSC’) and those in whom NIRS was started within two minutes after ROSC (‘post ROSC’). Initial rSO2 in the patients with no ROSC was generally very low (median 16 %, IQR 15–29 %). Initial rSO2 was also low in the five patients with ROSC in whom NIRS was started during CPR (15, 16, 22, 23 and 46 %, Table 2). The difference was not statistically significant (p = 0.312). In six patients NIRS monitoring could not be started pre-ROSC but immediately after ROSC. Initial rSO2 was substantially higher (54–85 %) in these patients as compared with patients with pre-ROSC NIRS monitoring (p = 0.006, Fig. 2).

In 5 patients ICU treatment was withdrawn due to severe hypoxic encephalopathy (n = 4) and multi-organ failure (n = 1). Withdrawal of treatment for hypoxic encephalopathy was done after repetitive neurological examination, neurophysiologcial, radiological and laboratory testing if available (including somatosensory evoked potentials (SSEP), neuro-specific enoloase (NSE), brain computed tomography (CT) and electroencephalography EEG) following a standardized pathway. Brain oxygen saturation measurements were not used for prognostic purposes.

Initial regional oxygen saturation and neurological outcome Five patients with NIRS recording during CPR reached ROSC. Two of those patients had a good outcome (CPC 1, both at discharge and at six months). The initial rSO2 of both of these two patients was 22 %. Three patients with ROSC in whom NIRS was recorded during CPR died during ICU stay. The initial rSO2 of these patients was 15, 16 and 46 %; Table 2). In six patients monitoring started approximately two minutes after ROSC. One patient had a good outcome (CPC1) and of the remaining five patients, four died during the ICU stay and one had CPC3 at ICU discharge and had died at six months follow-up. The patient with good outcome had a high initial post-ROSC rSO2 (80 %).

Discussion Our main findings are: (1) Patients with initially very low regional cerebral oxygen saturation (as low as 22 % determined by a commercially available near-infrared spectroscopy monitor) during out-of-hospital cardiac arrest and resuscitation may survive with good outcome. (2) Intial rSO2 during CPR obtained immediately after arrival of EMS was generally low and did not allow to predict ROSC or neurological outcome. (3) Immediately (<2 min) after ROSC, rSO2 was substantially higher at or close to physiological values (54-85 % in six patients).

Pre-ROSC rSO2 The very low regional frontal brain oxygen saturation observed in our study is in line with previous reports. For example, in an early report with NIRS during CPR, Newman and coworkers found no detectable cerebral oxygen saturation during CPR in all of sixteen subjects [11]. Parnia and coworkers also found very low initial rSO2 (15–21 %) determined by NIRS during CPR in 15 cardiac arrest patients. Increasing rSO2 with

Table 1 Baseline characteristics Post ROSC

Pre ROSC

No ROSC

Age (years) (mean (sd))

68 (9)

66 (7)

61(14)

Sex male n (%)

6 (100)

4 (80)

14 (78)

APACHE score (median [IQR])

28 [20, 36]

37 [20, 40]

Shockable rhythm n (%)

RESUSCITATION TODAY - AUTUMN 2016

Ventricular fibrillation

2 (33)

1 (20)

4 (22)

Asystolic

1 (17)

3 (60)

9 (50)

3 (50)

1 (20)

5 (27)

Time to ROSC (min) (median [IQR])

EMD

19 [11, 27]

12 [9, 16]

Total epinephrine dose (mg) (median [IQR])

2 [0.5, 4.25]

1 [1, 2]

7 [4, 9.5]

Haemoglobin (g/dl) (median [IQR])

12 [11, 14]

13 [12, 15]

Lactate (median [IQR])

29 [27, 45]

52 [43, 60]

Time on ventilator (hours) (median [IQR])

382 [164, 458]

212 [73, 388]

Length of ICU stay (days) (median [IQR])

17 [8, 20]

14 [3, 16]

Data are given as median and interquartile range (IQR) or absolute numbers and percent. ‘Post ROSC’ designates the group of patients in which NIRS was started shortly after ROSC, ‘pre ROSC’ designates the group with NIRS started during CPR and who achieved ROSC, ‘no ROSC’ the group with NIRS during CPR but no ROSC. APACHE Acute Physiology And Chronic Health Evaluation; OHCA out-of-hospital cardiac arrest; ROSC return of spontaneous circulation; ICU intensive care unit; EMD electromechanical dissociation; PaO2 arterial oxygen partial pressure; SO2 peripheral oxygen saturation; PaCO2 arterial carbon dioxide partial pressure; FiO2 fraction of inspired oxygen

EVIDENCE ongoing CPR was observed which was associated with ROSC in their study [12]. In another trial, Parnia and coworkers demonstrated low rSO2 during manual chest compression (median rSO2 24 %) and significantly higher values in patients treated with an automated chest compression device (median rSO2 53 %) [13]. Schewe and coworkers reported similar results [4]. Kämäräinen also demonstrated very low rSO2 during manual CPR which did not substantially increase by improving manual CPR technique [14]. In line with our results, Genbrugge et al. reported no significant difference between initial rSO2 in patients achieving ROSC compared to those who did not when NIRS was started during CPR on scene [5]. Taken together, these studies consistently show a very low cerebral oxygen saturation as measured by commercially available NIRS

monitors during cardiac arrest and CPR. Clearly, brain hypoxia during CPR causes severe hypoxic encephalopathy in many patients. However, when interpreting rSO2 measurements during CPR it needs to be kept in mind that compared to the cerebral metabolic rate of oxygen in an awake state the brain needs much less oxygen to simply maintain cell viability. Furthermore, regional brain rSO2 does not directly inform on the amount of oxygen delivered to the brain and thus low rSO2 obtained at a single time point cannot predict the extent of hypoxic encephalopathy. It may be, however, that integrating information on duration and extent of hypoxia measured by NIRS may allow for a largely reliable prediction of outcome and may be used in the future among other parameters in the decision to continue or stop resucitation efforts.

Table 2 Data of n = 29 patients included by EMS divided into NIRS during CPR without ROSC (n = 18), ROSC (n = 5) and NIRS started after ROSC (n = 6) rSO2 EMS data n = 29 rSO2 (%) rSO2 during CPR n = 23

Outcome Discharge

tROSC (min)

First rhythm

Age (years)

Sex

asystole

male

6 month

Pre ROSC n = 5 1

46 %

CPC 5

22 %

CPC 1

15 %

CPC 5

16 %

CPC 5

22 %

CPC 1

15 %

CPC 5

CPC 1

asystole

male

asystole

female

PEA

male

asystole

female

No ROSC n = 18 1 2

15 %

CPC 5

asystole

female

15 %

CPC 5

asystole

female

15 %

CPC 5

PEA

male

15 %

CPC 5

male

15 %

CPC 5

male

15 %

CPC 5

male

41 %

CPC 5

PEA

male

16 %

CPC 5

asystole

male

20 %

CPC 5

PEA

female

22 %

CPC 5

asystole

male

15 %

CPC 5

male

35 %

CPC 5

asystole

male

15 %

CPC 5

asystole

male

42 %

CPC 5

asystole

male

15 %

CPC 5

asystole

male

15 %

CPC 5

PEA

male

15 %

CPC 5

PEA

male

63 %

CPC 5

asystole

male

71 %

CPC 5

male

57 %

CPC 5

PEA

male

54 %

CPC 5

PEA

male

80 %

CPC 1

male

85 %

CPC 3

CPC 5

PEA

male

Post ROSC n = 6

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8 9

Initial rSO2, outcome, time to ROSC, first rhythm, age and sex are given

EVIDENCE Post ROSC rSO2 In our study, the six patients with rSO2 measurement started immediately after ROSC (<2 min) showed regional frontal brain oxygenation at or close to physiological values (54–85 %). The rapid increase of rSO2 following ROSC suggested by this finding is in line with previous reports. E.g., Genbrugge and coworkers demonstrated rSO2 changes from 25–30 % immediately pre-ROSC up to 60–70 % two minutes post-ROSC in a cardiac arrest patient [9]. Kämäräinen et al. found a median rSO2 of 60 % in seven patients eight minutes after ROSC [14]. Ito and coworkers found substantially higher rSO2 in cardiac arrest patients with detectable pulses (ROSC) upon hospital arrival (51 %) as compared to those without (19 %). Collectively, these studies indicate that rSO2 rapidly increases after ROSC to median/mean values close to physiological rSO2.

Initial rSO2 and outcome prediction In a recent large multicenter trial, Ito and coworkers found very low initial rSO2 (15 % as determined by a commercially available NIRS monitor, representing the lower measurement threshold) in three patients with good neurological outcome [6]. Only 29 out of 672 patients in this study had a good outcome. In contrast to our study with NIRS started on scene, Ito and coworkers started rSO2 measurements upon hospital arrival after EMS transfer with ongoing CPR. Termination of CPR is not allowed for EMS in Japan. Our cohort was collected in a large urban area with a short response time of EMS. Thus, it is very likely that in our study NIRS was started much earlier in the course of CPR than in the study by Ito and coworkers. A subset of patients in the study by Ito and coworkers had already achieved ROSC when NIRS was started upon hospital arrival which explains the more frequent finding of high initial rSO2 in their study [6]. Taken together, our study and the study by Ito and coworkers underscore that patients may recover with good neurological outcome despite very low frontal brain rSO2 recorded during CPR on scene as well as upon hospital arrival. Very recently, Nishiyama and coworkers reported a very large study on NIRS during CPR at hospital arrival. Their results indicate that the proportion of patients with good neurological outcome at the lowest measured initial rSO2 (15 %, the lower detection limit of the monitor) is very low. Although our patient cohort is smaller, our results indicate that initial rSO2

Fig. 2 Initial rSO2 (median and IQR) for patients in whom NIRS was started within two minutes after ROSC (‘post-ROSC’), patients in whom NIRS was started during CPR and who achieved ROSC (‘pre-ROSC’) and in patients during CPR who did not achieve ROSC (‘no ROSC’)

initial rSO2 are exceptional. Furthermore, we did not record the course of rSO2 during resuscitation until ROSC which would have allowed for am more detailed investigation. It is also possible that the cause of arrest may influence the relationship between rSO2 recorded during CPR and outcome. E.g., patients with respiratory arrest may have significant hypoxia already prior to the cardiac arrest which could influence the periode between cardiac arrest and irreversible neuronal damage. We did not record the time between collapse/emergency call and first NIRS recording with sufficient precision. This may influence the relationsship between initial rSO2 and outcome or chance of ROSC and it would be interesting to investigate this question in future studies. Calculation of regional brain oxygen saturation using noninvasive near-infrared spectroscopy is complex and results may differ between different commercially available NIRS-monitors due to different rSO2 calculation algorithms. The NIRS signal does not originate exclusively from brain tissue and therefore, confounding by extracerebral sources is possible. The sample volume within the brain contains arteries, capillaries and veins with different oxygen tensions. The composition of the sample volume varies from patient to patient. Thus, the absolute values for rSO2 reported in this study need to be interpreted with caution and do not represent average brain tissue oxygenation.

obtained during CPR at hospital arrival and initial rSO2 obtained during CPR on scene (in a setting with short EMS response time) bear different prognostic implications. Before NIRS started during CPR on scene may RESUSCITATION TODAY - AUTUMN 2016

Conclusion

be used for prediction of outcome and in decisions to terminate CPR, further large studies on the relationship between duration and extent of

Initial brain oxygen saturation is genearlly very low in cardiac arrest

regional brain hypoxia as measured by NIRS and outcome are needed.

patients immediately after arrival of EMS. Very low initial brain oxygen saturation is compatible with ROSC and with good neurological outcome and should not be regarded as an absolute poor prognostic sign.

Limitations Because ROSC is achieved in less than half of patients with cardiac

Declarations

arrest and less than half of those have had a good neurological outcome, the number of patients with good neurological outcome

Acknowledgments

included was small. Thus, we could not determine the distribution

We thank all supporting emergency physicians, paramedics and

of initial rSO2 during CPR in a large cohort of patients with good

emergency technicians serving the Berlin Fire Station 25 during the

neurological outcome. Larger studies are desirable to determine

trial. A special thank you to the emergency physicians S. Kaemper,

whether our two cases of good neurological outcome despite very low

S. Rademacher, A. Finn, R. Senf, L. Nibbe, F. Martens, D. Hasper, H.

EVIDENCE Gruß, J. Kruse, T. Bender, J. Stoll, J. Schefold, R. Koerner and to the paramedics G. Goerlitz, B. Bruckmoser, D. Gondar and S. Malek from the emergency physician staffed mobile intensive care unit (NEF 2505). Furthermore we would like to thank our ICU team, especially the nurses, for outstanding support during the trial and a special thank you to our study nurse Astrid Caemmerer for her tireless effort and support. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons. org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Competing interests This study received technical support (INVOS monitors and sensors) and financial support with a grant by COVIDIEN (USA) to cover costs over the study period. The industrial sponsor had no influence regarding the study protocol, inclusion of patients, final analyzing of the data and drafting of the manuscript. The study was investigator initiated. C. Storm has received remuneration for presentations, travel costs and partial technical or material support from Philips, C.R.BARD, Zoll, Medivance, COVIDIEN, Nonin Medical and a grant from the German Heart Foundation. C. Leithner has received remuneration for presentations and travel costs from C.R. BARD. Authors’ contributions CS, AW, JN and CL conceived of the study, participated in its design and coordination and helped to draft the manuscript. LT, SR and FL were responsible for data collection and data management. AK participated in the design of the study and performed the statistical

in out-of-hospital patients is associated with return of spontaneous circulation. Crit Care. 2015;19:112. 6. Ito N, Nishiyama K, Callaway CW, Orita T, Hayashida K, Arimoto H, et al. Noninvasive regional cerebral oxygen saturation for neurological prognostication of patients with out-of-hospital cardiac arrest: a prospective multicenter observational study. Resuscitation. 2014;85:778–84. 7. Fukuda T, Ohashi N, Nishida M, Gunshin M, Doi K, Matsubara T, et al. Application of cerebral oxygen saturation to prediction of the futility of resuscitation for out-of-hospital cardiopulmonary arrest patients: a single-center, prospective, observational study: can cerebral regional oxygen saturation predict the futility of CPR? The American journal of emergency medicine. 2014;32:747–51. 8. Nishiyama K, Ito N, Orita T, Hayashida K, Arimoto H, Beppu S, et al. Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study. Resuscitation. 2015;96:135–41. 9. Genbrugge C, Dens J, Meex I, Boer W, Jans F, De Deyne C. Cerebral saturation monitoring during cardiopulmonary resuscitation should be used as dynamic, rather than static, information. Resuscitation. 2013;84:e111–2. 10. Storm C, Leithner C, Krannich A, Wutzler A, Ploner CJ, Trenkmann L, et al. Regional cerebral oxygen saturation after cardiac arrest in 60 patients-A prospective outcome study. Resuscitation. 2014;85:1037–41. 11. Newman DH, Callaway CW, Greenwald IB, Freed J. Cerebral oximetry in out-of-hospital cardiac arrest: standard CPR rarely provides detectable hemoglobin-oxygen saturation to the frontal cortex. Resuscitation. 2004;63:189–94. 12. Parnia S, Nasir A, Shah C, Patel R, Mani A, Richman P. A feasibility study evaluating the role of cerebral oximetry in predicting return of spontaneous circulation in cardiac arrest. Resuscitation. 2012;83:982–5. 13. Parnia S, Nasir A, Ahn A, Malik H, Yang J, Zhu J, et al. A feasibility study of cerebral oximetry during in-hospital mechanical and manual cardiopulmonary resuscitation*. Crit Care Med. 2014;42:930–3. 14. Kamarainen A, Sainio M, Olkkola KT, Huhtala H, Tenhunen J, Hoppu S. Quality controlled manual chest compressions and cerebral oxygenation during in-hospital cardiac arrest. Resuscitation. 2012;83:138–42.

analysis. NO and TS participated in coordination of the trial and helped to draft the manuscript. All authors read and approved the final manuscript.

2. Parnia S. Cerebral oximetry - the holy grail of non-invasive cerebral perfusion monitoring in cardiac arrest or just a false dawn? Resuscitation. 2012;83:11–2. 3. Sanfilippo F, Serena G, Corredor C, Benedetto U, Maybauer MO, Al-Subaie N, et al. Cerebral oximetry and return of spontaneous circulation after cardiac arrest: A systematic review and metaanalysis. Resuscitation. 2015;94:67–72. 4. Schewe JC, Thudium MO, Kappler J, Steinhagen F, Eichhorn L, Erdfelder F, et al. Monitoring of cerebral oxygen saturation during resuscitation in out-of-hospital cardiac arrest: a feasibility study in a physician staffed emergency medical system. Scandinavian journal of trauma, resuscitation and emergency medicine. 2014;22:58.

RESUSCITATION TODAY - AUTUMN 2016

References 1. Genbrugge C, Boer W, Meex I, Jans F, Dens J, De Deyne C. Cerebral tissue saturation, the next step in cardiopulmonary resuscitation management? Crit Care. 2014;18:583.

5. Genbrugge C, Meex I, Boer W, Jans F, Heylen R, Ferdinande B, et al. Increase in cerebral oxygenation during advanced life support

NEWS Five presentations at AHS meeting provide new insights into non-invasive vagus nerve stimulation’s mode of action Basking Ridge, New Jersey: Five studies, covering both clinical and preclinical results, providing insight into the mode of action of non-invasive vagus nerve stimulation (nVNS) were presented at the American Headache Society (AHS) annual meeting (June 9-12). There is growing scientific consensus that the effect of vagus nerve stimulation on primary headache can be demonstrated via a number of underlying mechanisms of action (MOA). The first clinical study, from researchers at the Headache Research Unit of the University of Liège in Belgium, found that nVNS, using electroCore’s gammaCore device, is effective in stimulating the afferent vagal fibers (the nerve cells which carry the signals to the brain). The study concluded that, “The therapeutic effects reported with gammaCore® in primary headaches can thus be mediated by genuine activation of vagus nerve afferents.”

The same academic group from the University of Liège also presented the results of their clinical study into the effects of nVNS on habituation deficit, a phenomenon that is frequently observed in migraine patients, that is associated with a hyperexcitability state in the brain. By observing changes in response to visual evoked potentials[1] (VEP), and correlating the results with the clinical benefits observed among migraine patients, the group demonstrated that using the nVNS gammaCore device is associated with modulation of corticothalmic circuits in the brain, bringing their function back into the normal range. The next stage in this ongoing research is to determine if nVNS has a longterm effect, and if this normalization is truly predictive of therapeutic response. Another study from researchers at The City College of New York and the UCSD Center for Pain Medicine in San Diego was conducted in a computational model. The study showed that nVNS can produce electric fields and/or electric field gradients at sufficient amplitudes and depths within the neck to stimulate afferent fibers in the vagus nerve. The researchers concluded that, “The many clinical benefits of VNS with a surgically implanted stimulator can now be achieved non-invasively without the cost (around $30,000) and morbidity associated with an implanted stimulator”.

The final two presentations were of pre-clinical studies investigating the MOA of VNS in animal models of pain. The first study, from the NYU College of Medicine and Dentistry, investigated the effects of VNS on acute intracranial head pain. Their findings suggest the mechanism for the previously reported efficacy of nVNS in the abortive treatment of cluster headache by proving that stimulation of the cervical branch of the vagus nerve inhibits the activation of pain receptors in the main facial nerve. The researchers also suggested that their study could “validate this model of acute intracranial pain as a translational approach to optimize therapeutic efficacy,” meaning that their findings can be applied to clinical studies into nVNS and primary headache conditions. The second study, from Missouri State University, found that nVNS can stop the activation of sensory neurons implicated in the underlying pathology of migraine and temporomandibular joint disorders (TMJ). This study further confirms the results previously reported by Michael Oshinsky (Pain, 2014), which demonstrated the ability of nVNS to suppress excessive glutamate (an excitatory neurotransmitter associated with neuronal hyperexcitability, which is implicated in migraine and other pain conditions). Consequently, the researchers concluded, “VNS may be useful as a nonpharmacological therapy for treating episodic migraine and inhibiting pain associated with TMJ Syndrome (pain in the jaw bone)”. www.electrocore.com

Poor working conditions for junior doctors in the NHS harm patients RESUSCITATION TODAY - AUTUMN 2016

• Poor working conditions for junior doctors in the NHS are harmful to patients who need emergency surgery, new study highlights • Findings are one step towards explaining why some NHS hospitals suffer a high rate of patient mortality after emergency surgery • Study uses CQC and national in-patient survey data from Chelsea and Westminster Hospitals NHS Foundation; East Kent Hospitals University NHS Foundation Trust; Frimley Park Hospital NHS Foundation Trust; Northampton General Hospital NHS Trust; Sherwood Forest Hospitals NHS Foundation Trust

NEWS Poor conditions for junior doctors working in the NHS are harmful to patients who need emergency surgery, a new study has highlighted. The research from Birkbeck, University of London has discovered a significant disparity in the experiences of patients who have emergency surgery, comparing NHS hospitals with good and poor working conditions for junior doctors. The Birkbeck research was inspired by The Royal College of Surgeons of England’s emergency surgery policy briefing (https:// www.rcseng.ac.uk/government-relationsand-consultation/documents/RCS%20 Emergency%20surgery%20policy%20briefing. pdf) highlighting concerning variation across hospitals in the standards of emergency surgery care and the rate of patient mortality. The mortality rate after some types of emergency surgery is 4% in some hospitals yet in other hospitals as many as 42% of patients died after the same procedure. Organizational problems, such as poor levels of staffing within emergency contexts, and poor working conditions for junior doctors working in A&E are contributing factors. Birkbeck organizational psychologist, Dr. Caroline Kamau, conducted a naturalistic experiment using data taken from the national in-patient survey and Care Quality Commission (CQC) reports about junior doctors’ experiences in five randomly-selected English NHS trusts:

the issues are said by the CQC to be not effectively mitigating the risks to junior doctors.

• Increase the number of NHS consultants in A&E

In Northampton General, junior doctors spoke to the CQC of being brutally busy and the CQC wrote that the Trust lacked full compliance with mandatory training and personal development planning.

• Increase the number of NHS registrars and consultants with expertise in emergency surgery

The research shows how different variables interact in determining the quality of patients’ experiences. Stressing the importance of improving working conditions for junior doctors, the study author, Dr. Kamau, said: “Between 30% and 40% of emergency patients undergo surgery, which has an increased risk of serious complications and death yet junior doctors are often responsible for reviewing patients who go to emergency. Delays of diagnosis or investigation can be lethal. “Organizational support for junior doctors in the NHS is pivotal if we want to address these problems.” This is the first study to triangulate CQC data and in-patient data in this context. Among the study’s recommendations are:

• Give junior doctors inductions that speed up their decision-making about patients who need urgent surgery • Increase government funding for research into emergency surgery The report, titled Vulnerability of emergency surgery to the working conditions of new doctors was published 01.09.16 in The Bulletin of the Royal College of Surgeons of England. Yesterday it was announced that junior doctors are to stage five days of industrial action in the row over the controversial new contract for training medics. This research shows that improving working conditions for junior doctors in the NHS has a positive impact on patients. Dr. Kamau, who works within Birkbeck’s Department of Organizational Psychology, added: “Hospitals should listen to junior doctors and find ways of improving their working conditions. Hospitals that are supportive of their junior doctors end up with better patient experiences.”

• Chelsea and Westminster Hospitals NHS Foundation • East Kent Hospitals University NHS Foundation Trust • Frimley Park Hospital NHS Foundation Trust

• Sherwood Forest Hospitals NHS Foundation Trust The quality reports show that Chelsea and Westminster, Frimley Park and Sherwood Forest hospitals have good working conditions for junior doctors whereas in Northampton General and East Kent hospitals the conditions need improvement. Quality data show that East Kent hospitals need better staffing and training support for junior doctors, and their plans to improve

RESUSCITATION TODAY - AUTUMN 2016

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