Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial

This study compares the effectiveness of mechanical chest compression devices versus manual chest compressions for out-of-hospital cardiac arrest. The study enrolled 4471 eligible patients and found no evidence of improvement in 30-day survival with LUCAS-2 compared with manual compressions. The study concludes that widespread adoption of mechanical CPR devices for routine use does not improve survival.

Articles
www.thelancet.com Vol 385 March 14, 2015 947
Mechanical versus manual chest compression for
out-of-hospital cardiac arrest (PARAMEDIC): a pragmati
cluster randomised controlled trial
Gavin D Perkins, Ranjit Lall, Tom Quinn, Charles D Deakin, Matthew W Cooke, Jessica Horton, Sarah E Lamb, Anne-Marie Slowther,
Malcolm Woollard, Andy Carson, Mike Smyth, Richard Whitfi eld, Amanda Williams, Helen Pocock, John J M Black, John Wright, Kyee
Simon Gates, PARAMEDIC trial collaborators*
Summary
Background Mechanical chest compression devices have the potential to help maintain high-quality cardiopul
resuscitation (CPR), but despite their increasing use, little evidence exists for their eff ectiveness. We aimed
whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would impr
survival from out-of-hospital cardiac arrest.
Methods The pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARA
trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospita
arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and
semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, wh
randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression
manual chest compressions according to the fi rst trial vehicle to arrive on scene. The primary outcome was s
30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those
the primary outcome were masked to treatment allocation. Masking of the ambulance staff who deli
interventions and reported initial response to treatment was not possible. The study is registered wi
Controlled Trials, number ISRCTN08233942.
Findings We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the contr
between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest co
and 11 (<1%) patients in the control group received LUCAS-2. In the intention-to-treat analysis, 30 day surviv
in the LUCAS-2 group (104 [6%] of 1652 patients) and in the manual CPR group (193 [7%] of 2819 patients; ad
ratio [OR] 0·86, 95% CI 0·64–1·15). No serious adverse events were noted. Seven clinical adverse events were
the LUCAS-2 group (three patients with chest bruising, two with chest lacerations, and two with blood in mou
incidents occurred during operational use. No adverse or serious adverse events were reported in the manua
Interpretation We noted no evidence of improvement in 30 day survival with LUCAS-2 compared with
compressions. On the basis of ours and other recent randomised trials, widespread adoption of mechanical CP
devices for routine use does not improve survival.
Funding National Institute for Health Research HTA – 07/37/69.
Copyright © Perkins et al. Open Access article distributed under the terms of CC BY.
Introduction
The burden of cardiac arrest out of hospital is
substantial, with an estimated 424 000 cardiac arrests
occurring each year of about in the USA1 and 275 000 in
Europe.2 As few as one in 12 victims of cardiac arrest out
of hospital survive to return home.3,4 High-quality chest
compressions of suffi cient depth5 and rate,6 with full
recoil of the chest between compressions7 and avoidance
of interruptions8 are crucial to survival. Maintenance
of high-qualitycompressionsduring out-of-hospital
resuscitation is diffi cult because of the small number of
crew present, fatigue, patient access, competing tasks
(eg, defi brillation,vascularaccess)and diffi cultyof
performing resuscitation in a moving vehicle.9
Mechanical compression devices suitable for use in the
pre-hospital environment have been developed to automate
and potentiallyimprovethis process.At the time of
initiating this study, one large randomised trial of a load
distributing band mechanical device had been done and
was terminated early because of the worsened long-term
outcomes in patients allocated to mechanical compression.10
The subsequentCochranereviewreportedinsuffi cient
evidence to conclude that mechanical chest compressions
are associated with benefi t or harm and their widespread
use is not supported.11 Since then, two further large
randomised effi cacy trials have been reported. The CIRC
trial12 assessed the load distributing band and reported
it was equivalent to manual cardiopulmonary resuscitation
Lancet 2015; 385: 947–55
Published Online
November 16, 2014
http://dx.doi.org/10.1016/
S0140-6736(14)61886-9
See Comment page 920
*Collaborators listed at end
of paper
Warwick Clinical Trials Unit,
University of Warwick,
Coventry, UK
(Prof G D Perkins MD, R Lall PhD,
Prof M W Cooke PhD,
J Horton MSc,
Prof S E Lamb DPhil,
A-M Slowther DPhil,
M Smyth MSc, Prof S Gates PhD);
Heart of England NHS
Foundation Trust,
Birmingham, UK,
(Prof G D Perkins); Surrey
Peri-operative Anaesthesia
Critical care collaborative
Research Group, Faculty of
Health and Medical Sciences,
University of Surrey, Guildford
UK (Prof T Quinn M Phil,
Prof M Woollard MPH,
Prof C D Deakin MD); South
Central Ambulance Service
NHS Foundation Trust,
Otterbourne, UK
(Prof C D Deakin,H Pocock MSc,
J J M Black FCEM); NIHR
Southampton Respiratory
Biomedical Research Unit,
University Hospital
Southampton NHS Foundation
Trust, Southampton
Hampshire (Prof C D Deakin);
University of Oxford, Oxford,
UK (Prof S E Lamb); West
Midlands Ambulance Service
NHS Foundation Trust, Brierley
Hill, UK (A Carson FRCGP,
M Smyth); Welsh Ambulance
Services NHS Trust,
Denbighshire, Wales, UK
(R Whitfi eld BSc, A Williams MA);
North East Ambulance Service
NHS Foundation Trust,
Newcastle upon Tyne, UK
(J Wright FCEM, K Han FCEM);
and Royal Victoria Infi rmary,
Newcastle upon Tyne, UK
(J Wright)

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948 www.thelancet.com Vol 385 March 14, 201
Correspondence to:
Prof Gavin Perkins, Warwick
Clinical Trials Unit, University of
Warwick, Coventry CV4 7AL, UK
[e-mail]
(CPR). The LINC trial13 assessed the LUCAS device and
concluded that mechanical CPR did not result in improved
outcomes compared with manual CPR.13
Previous trials were designed as effi cacy (explanatory)
trials, which aim to answerthe question“Can this
intervention work under ideal conditions?”. We sought to
study mechanical CPR use under real life conditions, and
therefore adopted a pragmatic design for the pre-hospital
randomised assessment of a mechanical compression
device in cardiac arrest (PARAMEDIC) trial. The trial
soughtto assesswhetherLUCAS-2 was betterthan
manual CPR for the improvement of 30 day survival
in adults receivingresuscitationfor non-traumatic,
out-of-hospital cardiac arrest.
Methods
Trial design and participants
The PARAMEDIC trial was a pragmatic,cluster
randomised trial, with ambulance service vehicles as the
unit of randomisation.The trial protocolhas been
published previously.14
The trial was done in partnership with four UK National
Health Service (NHS) Ambulance Services (West Midlands,
North East England, Wales, South Central). These sites
serve a total population of 13 million people sprea
62 160km². We selected91 ambulancestationsfor
participation based on their location (urban and semi-ur
settings, representing 25% of stations). A dispatch cent
in each region coordinated the emergency response. Th
nearest availablerapid responsevehicle (RRV) or
ambulance was dispatched to cases of suspected c
arrest. Back-up was provided by a second vehicle as soo
possible. If there was clear evidence that life was extinc
rigor mortis, post-mortem staining; see appendix for ful
details) or the patient had a do-not-attempt-resuscit
order, ambulance staff were authorised to recognise de
and withhold CPR. Where resuscitation was indicate
ambulance staff had been trained in advanced airw
management,drug administration,and externaldefi b-
rillation, and follow standardised national guidelines bas
on the European Resuscitation Council Guide lines.15,16 If
the patient did not respond despite full ALS intervention
and remained asystolic for more than 20 min then
resuscitation attempt could be discontinued. Unless the
criteria were met, resuscitation was continued and
patient was transportedto the nearestemergency
departmentwith continuousCPR. CPR quality and
feedbacktechnologywas not availablein any of the
participating ambulance services.
We chose broad eligibility criteria, indicatingthe
pragmatic nature of the trial. Individual patients we
included in the study if a trial vehicle was the fi rs
ambulance service vehicle on scene, the patient was in
cardiac arrest outside of a hospital, resuscitation w
attempted, and the patient was known or believed to be
aged 18 years or older. Exclusion criteria were card
arrest caused by trauma, and known or clinically
apparent pregnancy.
Ambulanceservicesrecordedcardiac arrest data
according to variables contained in the Utstein template17
Every ambulance service submitted these data to a cen
trial database.
Enrolment proceededwith a waiver of informed
consent, in line with the Mental Capacity Act 2005. The
trial team contacted patients who were discharged from
hospital to let them know of their enrolment and to invit
them to take part in the follow-up3 months and
12 months after cardiac arrest. Those willing to take pa
provided written informed consent. For those who d
not have capacity, a personal consultee completed
questionnaires on behalf of the patient.
The Coventry Research Ethics Committee (referenc
09/H1210/69)approvedthe study,and Universityof
Warwick,UK sponsoredit. The study was done in
accordance with the principles of Good Clinical Practice
and the Mental Capacity Act (2005).
Randomisation and masking
Because the number of LUCAS devices available to the
trial was limited to 143, we used a ratio of about 1 LUCA
to 2 control to optimise effi ciency. Individual ambulanc
See Online for appendix
Figure 1: Trial profi le
*Seven met more than one exclusion criteria. †Reasons LUCAS-2 not used: 78 because of crew not trained;
168 because of crew error; 26 no device in vehicle; 102 unsuitable patients (58 patient too large, 22 patient too
small, 22 other reason–eg, chest deformity), 14 device issues, 140 not possible to use device; 110 reason unknown.
Reasons for LUCAS-2 use in control group were crew error.
418 clusters recruited
11171 patients from emergency
incidents attended
4689 assessed for eligibility
6482 recognition of life extinct or
no resuscitation attempted
218 excluded*
2 pregnant
107 trauma
107 aged younger than 18 years
9 not out of hospital4471 enrolled
147 clusters allocated to LUCAS-2 group
1652 patients allocated to LUCAS-2 group
985 received LUCAS-2 chest compression
638 received manual chest compression†
29 intervention received unknown
271 clusters allocated to control group
2819 patients allocated to control group
2808 received manual chest compression
11 received LUCAS-2 chest compression
1 unknown survival status
1652 followed up to 3 months and 12 months
1652 analysed
2818 followed up to 3 months and 12 months
2818 analysed

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vehicles(clusters)were assignedwith a computer-
generated randomisation sequence, which stratifi ed by
station and vehicle type (ambulance or RRV).
Individual patients were allocated to the LUCAS-2 or
control (standardmanual chest compression)group
according to the fi rst trial vehicle on scene. We obtained
information from ambulance services on all potential
cardiac arrests attended by trial vehicles, and included
all eligible patients in the trial, thereby minimising
selection bias.
Ambulance dispatch staff were unaware of the
randomised allocations. Masking of ambulance clinicians
was not possible,since they gave the intervention.
Vehicles randomly assigned to LUCAS-2 were identifi ed
to ambulance clinical staff at the start of the shift during
vehicle checks and through stickers contained in the cab
of the vehicle and on the outside of the vehicle. We
extractedshort-termoutcomesfrom ambulanceor
hospital records. We obtained survival status at 30 days,
3 months, and 12 months from the NHS Information
Centre’s central death register. Trial staff who assessed
patient neurologicaloutcomewere unawareof the
randomised allocation or the treatment received.
Procedures
Paramedics seconded to work on the trial and clinical
educator staff trained all operational ambulance staff to
use LUCAS-2. Because of the vehicle movements and
staff rotations, staff serviced vehicles that were randomly
assigned to both LUCAS-2 and manual groups. Training
was carefully designed by the ambulance services on the
basis of the manufacturers guidance. Because of the
pragmatic design of this trial, training was developed in
accordance with the process by which new technology
would be introducedin routine practiceinto NHS
Ambulance Services. This preparation included access to
online training resources and included 1–2 h face-to-face
training, updated annually. Training covered the study
protocol and procedures, how to operate the LUCAS-2
device, and the importance of high-quality CPR. Training
included hands-on device deployment practice, with a
resus citation manikin, and emphasised the importance
of rapid deployment with minimum interruptions in
CPR. A competencychecklistwas completedbefore
authorising staff to deploy the LUCAS-2 device. Research
paramedics reviewed all cases and provided feedback to
individual staff as required. The rate of device use and
reasonsfor non-usewere fed back to participating
services on a quarterly basis.
LUCAS-2 (Physio-Control Inc/Jolife AB, Lund, Sweden)
provides chest compressions between 40–53 mm in depth
(according to patient size) at a rate of 102 min–¹ and
ensures full chest recoil between compressions and an
equal time in compression and decompression. In the
LUCAS-2 group, staff initiated manual CPR and switched
the device on. Once powered up manual compressions
were paused briefl y while the back plate was inserted.
CPR was restarted while the central arms were positioned
until locked in place, suction cup was deployed and device
activated.After this procedure,ECG monitoringwas
For the online training
resources see http://www.
warwick.ac.uk/go/paramedic
LUCAS-2
(n=1652)
Manual CPR
(n=2819)
Age, years (mean [SD]) 71·0 (16·3) 71·6 (16·1)
Male 1039 (63%) 1774 (63%)
Aetiology
Presumed cardiac 1417 (86%) 2445 (87%)
Respiratory 125 (8%) 191 (7%)
Submersion 5 (<1%) 7 (<1%)
Unknown 48 (3%) 74 (3%)
Other (non-cardiac) 57 (3%) 102 (4%)
Location
Home 1336 (81%) 2336 (83%)
Public place 225 (14%) 362 (13%)
Other 91 (6%) 121 (4%)
Witnessed cardiac arrest 1001 (61%) 1749 (62%)
Bystander 704 (43%) 1223 (43%)
EMS 250 (15%) 449 (16%)
Non-EMS health care 47 (3%) 75 (3%)
Not known 0 2 (<1%)
Bystander CPR before EMS arrival
CPR n (%) 716 (43%) 1238 (44%)
Not known 90 (5%) 168 (6%)
Median time from emergency call
to vehicle arrival, min (IQR)
6·5 (4·8–9·1) 6·3 (4·6–9·2)
Initial rhythm
VF 364 (22%) 597 (21%)
VT 12 (1%) 18 (1%)
PEA 398 (24%) 707 (25%)
Asystole 824 (50%) 1384 (49%)
Not known 54 (3%) 113 (4%)
Defi brillation before EMS arrival19 (1%) 40 (2%)
Treatment of cardiac arrest
Intravenous drugs given 1366 (83%) 2255 (80%)
Not known 8 (<1%) 14 (<1%)
Intubation
Intubated 749 (45%) 1297 (46%)
Not known 33 (2%) 48 (2%)
LMA or supraglottic airway device
LMA or supraglottic airway device
used
435 (26%) 736 (26%)
Not known 29 (2%) 47 (2%)
Transport to hospital 1099 (67%) 1868 (66%)
Transport to hospital status at
handover
ROSC 377 (23%) 658 (23%)
CPR in progress 640 (39%) 1081 (38%)
Unknown 82 (5%) 129 (5%)
Data are n (%) or mean (SD). CPR=cardiopulmonary resuscitation.
EMS=emergency medical services. VF=ventricular fi brillation. VT=ventricular
tachycardia. PEA=pulseless electrical activity. LMA=laryngeal mask airway.
ROSC=return of spontaneous circulation.
Table 1: Baseline characteristics and treatment

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established and LUCAS-2 was briefl y paused to check the
ECG rhythm. If the patient was in a shockable rhythm
LUCAS-2 was restarted and defi brillation was attempted
with continuous mechanical CPR.
Patients in the control group received manual CPR
aiming for a target compression depth of 50–60 mm,
rate 100–120 min–¹, full recoil between compressions
and an equal time in compression and decompression
in line with guidelines. CPR was started on arrival and
ECG monitoring established. Chest compressions were
paused briefl y to allow rhythm analysis and if
appropriate,attempteddefi brillation.Both groups
received compression to ventilation ratio of 30:2 before
intubationand continuouscompressionswith asyn-
chronous ventilation after intubation.
Outcomes
The primary outcome of the study was survival to 30 days
after the cardiac arrest event. The main secondary clinical
outcomes were survived event (return of spontaneous
circulation [ROSC] sustaineduntil admission and
transfer of care to medical staff at the receiving hospital),
survival to 3 months, survival to 12 months, and survival
with favourable neurological outcome at 3 months. The
initial trial protocol originally specifi edsurvival to
hospital dischargeas an additionaloutcome;this
outcome is not reported here because survival to 30 days
is more clinically meaningful, and these data could not
be obtainedfrom all hospitalsincludedin the trial
because of logistical and governance diffi culties. We h
reportedROSC as an additional(non-prespecifi ed)
outcome since it is part of the Utstein template.17
We defi nedfavourableneurologicaloutcomeas a
Cerebral Performance Category (CPC) score17 of 1 or 2 at
3 months. CPC was extracted from medical records
assessed at a face-to-face visit done by research staff .
Statistical analysis
At the time of the design of this study, there were
randomised trials using the LUCAS device on which to
base the likely treatmenteff ect.We determinedthe
minimally important diff erence to our decision makers
(the NHS) through discussion with partner ambulanc
services and subsequent agreement with the funder. Th
study had 80% power to fi nd a signifi cant result
threshold two-sided p value of 0·05) if the incidence of
survival to 30 days was 5% in the manual CPR group an
7·5% in the LUCAS-2 group. Using an intracluster
correlation coeffi cient of 0·01 to allow for clustering, a
a cluster size of 15, we aimed to recruit 245 clust
(3675 patients) into the trial.
The target sample size was revised in September, 201
after recruitment of 2469 patients, to take account of th
frequency of use of LUCAS-2 and updated information
on the cluster size. With the agreement of the Dat
Monitoring Committee and the Trial Steering Committee
we increased the target sample size to 4344 patients. W
estimated this sample size to have a suffi cient number
cases of LUCAS-2 use to maintain the originally specifi e
power. The sample size re-estimation did not use a
information from comparisons between the trial groups.
The primary analysis was by intention to treat. Th
analysis explores if the treatment works under the usua
conditions, with all the noise inherent therein. We used
complier averagecausal eff ect(CACE) analyses,to
estimate the eff ect in cardiac arrest where the protocol
followed.18,19
CACE estimates the treatment eff ect in peop
randomlyassignedto the interventionwho actually
received it, by comparing compliers in the interven
group with those participants in the control group
would have been compliers if they had been alloca
to the interventiongroup. This analysisretainsthe
advantages of randomisation and avoids introducing bia
hence CACE is preferred to per-protocol analysis. We did
two CACE analyses, defi ning compliers in diff erent way
In CACE1, we treated as non-compliant those cases
which LUCAS-2 was not used for unknown or trial-relate
reasons that would not occur in real-life clinical practice
(eg, crew were not trainedin trial procedures,crew
misunderstood the trial protocol, the device was missing
from the vehicle). This analysis omits trial-related non-u
and might be a better estimate of the treatment eff ect
real-world clinical practice analysis by intention to treat
the CACE2 analysis, we only treated as compliant those
LUCAS-2
(n=1652)
Control
(n=2819)
Unadjusted OR
(95% CI)
Adjusted OR
(95% CI)
Survival to 30 days
Survived to 30 days 104 (6%) 193 (7%) 0·91 (0·71–1·17)0·86 (0·64–1·15)
Not known 0 1 (<1%) ·· ··
ROSC
ROSC 522 (32%) 885 (31%) 1·02 (0·89–1·16)0·99 (0·86–1·14)
Not known 58 (4%) 82 (3%) ·· ··
Survived event
Survived event 377 (23%) 658 (23%) 0·97 (0·83–1·14)0·97 (0·82–1·14)
Not known 82 (5%) 129 (5%) ·· ··
Survival to 3 months
Survived to 3 months 96 (6%) 182 (6%) 0·89 (0·69–1·15)0·83 (0·61–1·12)
Not known 0 1 (<1%) ·· ··
Survival to 12 months 89 (5%) 175 (6%) 0·86 (0·60–1·12)0·83 (0·62–1·11)
Survival with favourable
neurological outcome (CPC 1–2)
77 (5%) 168 (6%) 0·77 (0·59–1·02)0·72 (0·52–0·99)
CPC ·· ··
1 67 (4%) 153 (5%) ·· ··
2 10 (1%) 15 (1%) ·· ··
3 14 (1%) 10 (<!%) ·· ··
4 2 (<1%) 1 (<1%) ·· ··
5 1556 (94%) 2636 (94%) ·· ··
Not known 3 (<1%) 4 (<1%) ·· ··
Data are n (%) unless otherwise indicated. OR=odds ratio. ROSC=return of spontaneous circulation. CPC=cerebral
performance category score.
Table 2: Outcomes

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cases in which LUCAS-2 was actually used, and this
analysis therefore estimates effi cacy—ie, the treatment
eff ect in patients who received LUCAS-2.
For intention-to-treatanalyses,we used fi xed-eff ect
logistic regressionmodelsto obtain unadjustedand
adjusted odds ratios (ORs) and 95% CIs. The prespecifi ed
covariates used in the adjusted models were age, sex,
response time, bystander CPR, and initial rhythm. We
attemptedadjustingfor the clusteringdesign using
multilevel logistic models (using the GLIMMIX
procedure with logit link function based on the binomial
distribution). Because of the extremely low survival rates
in each cluster (vehicle), the multilevel models could not
be fi tted with the vehicle random eff ect since this eff ect
was not estimable. For this reason, we assumed that the
intracluster correlation coeffi cient was negligible (0·001)
and ordinary logistic regressions were fi tted. We also did
prespecifi ed subgroup analyses, by: (1) initial rhythm
(shockable vs non-shockable); (2) cardiac arrest witnessed
versus not witnessed; (3) type of vehicle (RRV versus
ambulance); (4) bystander CPR versus no bystander CPR;
(5) region, and (6) aetiology(presumedcardiac,or
non-cardiac); (7) age and (8) response time. We fi tted
logistic regressionmodels for the primary outcome
measure with the inclusion of an interaction term to
examine whether the treatment eff ect diff ered between
the subgroups. Age and response times are continuous
variablesand we assessedthese using multivariate
fractional polynomials.
We did all analyses using Statistical Analysis Software
(SAS) version 9·3 ( SAS Institute, Marlow, UK). This
trial is registeredon the International Standard
Randomised Controlled Trial Number Register, number
ISRCTN08233942.
Role of the funding source
The funder had no role in study design, data collection,
data analysis,data interpretation,or writing of the
report. RL had full access to all data in the study. GDP
and SG had fi nalresponsibilityfor the decisionto
submit for publication.
Results
We recruited 418 emergency vehicles (287 dual-manned
ambulancesand 131 single-mannedrapid response
vehicles) and randomly assigned them to either the
LUCAS-2 group (147 clusters) or the control group
(271 clusters; ratio 1:1·8; fi gure 1). In the 3 years of the
study, individual ambulance staff attended on average
4·1 (3·6) arrests in the control group and 3·0 (2·3) in
the LUCAS group.
The trial ran between April 15, 2010, and June 10, 2013
(with a 12 months’ follow-up) during which time trial
vehicles attended 11 171 emergency incidents (fi gure 1).
The trial fi nished when the revised target sample size
was exceeded.Cardiac arrest was confi rmedand
resuscitation attempted in 4689 cases of which 218 cases
were ineligible and excluded. The proportion of arrests
for which resuscitation was attempted did not diff er
between groups (1737 [41%] of 4192 for the LUCAS-2
group; 2953 [42%] of 6980 for the control group).
4471 patients were enrolled in the study. 985 (60%) of
the 1652 patientsin the LUCAS-2 group received
mechanical chest compression. The reasons for non-use
of LUCAS-2 were trial related(n=272),not possible
(n=256), or unknown (n=110; fi gure 1). We did not note
any major imbalances in baseline characteristics between
the trial groups (table 1). One patient in the control group
was lost to follow-up. No patient requested to withdraw
their data from the study.
For the primary outcome, 30 day survival was similar
in the LUCAS-2 and control groups (104 [6%] of patients
in the LUCAS-2 group, 193 [7%] of patients in the control
group, adjusted OR 0·86 [95% CI 0·64–1·15]; table 2)
The proportion of patients achieving any ROSC and
sustainedROSC with spontaneouscirculationuntil
admission and transfer of care to the medical staff at the
receiving hospital (survived event) was very similar in
the two groups (table 2). Survival at 3 months was also
similar to the primary outcome, indicating that little
mortality occurs between 30 days and 3 months.
The number of patients with a favourable neurological
outcome (CPC 1 or 2) was lower in the LUCAS-2 group
than in the control group (table 2).
Both CACE analyses had similar results to those of
the intention-to-treat analysis and are presented in
table 3. LUCAS-2 had almost no eff ect on ROSC and
survival of event, and 30 day survival did not diff er
between groups. The ORs for 30 day survival were
similar to those for the intention-to-treat analysis, but
the 95% CIs were slightly wider (table 2). However,
survival with CPC1-2 was lower in the LUCAS-2 group
CACE 1 CACE 2
LUCAS-2 Control OR (95% CI) LUCAS-2 Control OR (95% CI)
Survival to 30 days 81/1241 (7%) 153/2155 (7%) 0·92 (0·69–1·21) 50/985 (5%) 99/1710 (6%) 0·87 (0·61–1·23)
CPC 1–2 62/1238 (5%) 142/2151 (7%) 0·76 (0·56–1·03) 38/983 (4%) 101/1701 (6%) 0·65 (0·45–0·96)
Survived event 297/1241 (24%) 537/2026 (27%) 0·90 (0·77–1·06) 232/985 (24%) 415/1704 (24%) 0·97 (0·81–1·16)
ROSC 410/1212 (34%) 702/2104 (33%) 1·01 (0·88–1·17) 318/971 (33%) 538/1680 (32%) 1·02 (0·87–1·19)
CPC=cerebral performance category score. ROSC=return of spontaneous circulation. CACE=complier average causal eff ect.
Table 3: CACE analyses

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952 www.thelancet.com Vol 385 March 14, 201
than in the control group in both CACE analyses.
The appendix includes patient characteristics for the
CACE analyses.
Subgroup analyses according to whether the arrest was
witnessed, type of vehicle (ambulance or solo responder
car), whether the patient receivedbystanderCPR,
aetiology, and region showed no signifi cant diff erence in
30 day survival between the subgroups (table 4).
The subgroup analysis by initial rhythm showed a
diff erence in treatment eff ect between patients with a
shockableinitial rhythm and those with PEA or
asystole; survival was lower in the LUCAS-2 group in
those with shockableinitial rhythms than in the
control group.
Seven clinical adverse events were reported in the
LUCAS-2 group (three events of chest bruising, two of
chest laceration, and two of blood in mouth). No serious
adverseevents were reported.15 device incidents
occurredduring operationaluse (four incidents in
which alarms sounded,seven in which the device
stopped working, and four other device incidents). No
adverse or serious adverse events were reported in the
control group.
Discussion
In this pragmatic,cluster randomised trial, the
introduction of LUCAS-2 did not improve the primar
outcome of survival to 30 days. Meta-analysis of th
present study’s fi ndings alongside the results of th
two previous randomised trials including the LUCAS
mechanicalCPR device showed no evidence of
superiority in 30 day survival, survival to discharge
neurological function at 3 months (panel, fi gure 2).
This study was designed to assess the eff ectiveness o
LUCAS-2 when implemented in a real life setting. A
such it diff ered from recent industry sponsored effi cac
LUCAS-2 Control OR (95% CI)
Initial rhythm
VF or VT 69/376 (18%)148/615 (24%)0·71 (0·52–0·98)*
PEA or asystole24/1222 (2%) 30/2090 (1%)1·38 (0·80–2·36)
Rhythm not
known
54 113 ··
Witnessed status
Witnessed 89/1001 (9%)163/1749 (9%)0·96 (0·73–1·25)
Not witnessed 10/528 (2%) 21/864 (2%) 0·78 (0·36–1·66)
Witnessed status
not known
123 205 ··
Bystander CPR
Given 42/716 (6%) 68/1238 (5%)1·07 (0·72–1·59)
Not given 59/846 (7%) 115/1413 (8%)0·86 (0·61–1·17)
Not known 90 167 ··
Type of vehicle
Ambulance 60/1063 (6%)127/1773 (8%)0·78 (0·56–1·06)
Rapid response
car
44/589 (7%) 66/1045 (6%)1·20 (0·81–1·78)
Region
A 16/186 (9%) 23/357 (6%) 1·37 (0·70–2·66)
B 9/148 (6%) 33/359 (9%) 0·64 (0·30–1·37)
C 19/346 (5%) 22/352 (6%) 0·87 (0·46–1·64)
D 60/972 (6%) 115/1750 (7%)0·94 (0·68–1·29)
Aetiology
Presumed
cardiac
91/1417 (6%)173/2445 (7%)0·90 (0·69–1·17)
Other 9/130 (7%) 7/198 (4%) 2·03 (0·74–5·59)
Data are n/N (%) unless otherwise indicated. VT=ventricular tachycardia.
PEA=pulseless electrical activity. CPR=cardiopulmonary resuscitation.
VF=ventricular fi brillation. *Interaction eff ect of subgroup p<0·05.
Table 4: Subgroup analyses for primary outcome (30 day survival)
Panel: Research in context
Systematic review
We searched PubMed and The Cochrane Library from 200
to September, 2014, for randomised trials assessing LUC
for out of hospital cardiac arrest, using a combination of
(LUCAS, LUCAS-2, cardiac arrest, mechanical chest
compression, mechanical CPR) and medical subject head
terms (out-of-hospital cardiac arrest; death, sudden, card
heart arrest). We identifi ed two randomised trials: LINC,13
which was sponsored by the manufacturer of LUCAS and
recruited 2593 patients, and a much smaller pilot study20
done by the same investigators. We assessed bias risk of
trials using the Cochrane riskof bias method. Both of the
included trials were at low risk of bias for randomisation
methods, completeness of data, and selective reporting.
Masking of clinicians, participants, and outcome assessm
was not possible, but mortality and CPC score were very
unlikely to have been infl uenced by knowledge of trial
allocations. We noted some important diff erences betwe
LINC and PARAMEDIC. First, the intervention assessed in
LINC was a new treatment algorithm including mechanica
chest compression, whereas in PARAMEDIC, mechanical
chest compression was simply used to replace manual ch
compression. Second, survivors in LINC were treated with
hypothermia, whereas in PARAMEDIC post-resuscitation c
was given according to hospitals’ usual practice.
Interpretation
Meta-analysis of the outcomes survived event and surviv
hospital discharge or 30 days showed no evidence of
inconsistency between the three trials’ results, and no ev
of improvement with LUCAS (survived event odds ratio [O
1·00, 95% CI 0·90–1·11; survival OR 0·96, 0·80–1·15). The
two trials that reported survival with CPC 1–2 had inconsi
results (I²=69%), but overall did not suggest that outcom
were better with LUCAS than with manual chest compres
(random eff ects model OR 0·93, 0·64–1·33). The reasons
the inconsistency are unclear, but could be related to the
diff erences between the trials, particularly in relation to
implementation strategies adopted. PARAMEDIC supports
fi nding from LINC that use of LUCAS does not lead to an
improvement in survival, but additionally found that
neurological outcomes might be worse.

Articles
www.thelancet.com Vol 385 March 14, 2015 953
trials12,13 which included more intensiveinitial and
re- training, a run-in period; and in one study,12 a
statistical inclusion phase whereby patients were
excluded from analysis if quality of implementation fell
below a predefi ned threshold. Our pragmatic approach
to training, developedby experiencedambulance
training staff ,portrayedthe training that would be
delivered when rolling out new technology across UK
ambulanceservices. In this setting, the average
ambulance paramedic only encounters one to two cardiac
arrests annually21 and CPR update training is provided
annually, so it is unlikely that individuals became expert
in the use of the device.
The success of implementationis particularly
importantwhen balancingthe benefi tversus harm
potentialfor mechanicalchest compressiondevices
since interruptionsin CPR and delays in device
deploymentare a major factor that can impact
outcomes.22 In the present study 985 (60%) of
1652 patients randomly assigned to LUCAS received the
allocated intervention. While some cases of non-use
were due to patient-related and device-related factors, a
proportion (15%) arose because of diffi culties inherent
with implementationof new equipment and the
training and quality issues associated with this. Another
key diff erence between our study and other recent trials
was the absence of CPR feedback technology in the
participating ambulance services. CPR feedback devices
allow the measurement and adjustment of CPR quality
at the bedside.23 Although internationalguidelines
publishedin 201024 suggestedthe devicescould be
considered as part of an overall strategy to improve CPR
quality, their adoption into clinical practice has been
variable. The scarcity of this technology limited our
ability to report on the quality of CPR and monitor the
performanceof our implementationstrategy.These
fi ndings serve to highlight the potential limitations of
expecting the fi ndings from effi cacy trials to translate to
real life practice without applying the same degree of
rigor, attentionand assessmentapplied during the
index trials.
The sample size was increased to maintain the power
of the study on the basis of the rate at which the
intervention was used in practice. The intention-to-treat
Figure 2: Meta-analysis of the outcomes survived event and survival to hospital discharge or 30 days
(A) Survival to discharge or 30 days. (B) Survived event. (C) Survival with CPC 1–2.
Favours manualFavours LUCAS
00·5 0·7 1·5 2·0
LUCAS
A
Smekal 2011
LINC
PARAMEDIC
Total (95% CI)
Total events
Heterogeneity: χ2=0·43, df=2 (p=0·81); I2=0%
Test for overall effect: Z=0·49 (p=0·62)
Events
6
112
104
222
Total
75
1286
1652
3013
Manual
7
109
193
309
Events
72
1275
2818
4165
Total
2·7%
41·6%
55·7%
100·0%
Weight
Odds ratio
M–H, fixed, 95% CI
2011
2013
2014
Year
0·81 (0·26–2·53)
1·02 (0·77–1·34)
0·91 (0·71–1·17)
0·96 (0·80–1·15)
LUCAS
B
Smekal 2011
LINC
PARAMEDIC
Total (95% CI)
Total events
Heterogeneity: χ2=0·39, df=2 (p=0·82); I2=0%
Test for overall effect: Z=0·02 (p=0·99)
Events
18
366
377
761
Total
75
1300
1570
2945
Manual
15
357
658
1030
Events
72
1289
2690
4051
Total
1·8%
40·4%
57·8%
100·0%
Weight
Odds ratio
M–H, fixed, 95% CI
2011
2013
2014
Year
1·20 (0·55–2·61)
1·02 (0·86–1·21)
0·98 (0·84–1·13)
1·00 (0·90–1·11)
LUCAS
C
Survival to discharge or 30 days
Survived event
Survival with CPC 1–2
LINC
PARAMEDIC
Total (95% CI)
Total events
Heterogeneity: τ2=0·05, χ2=3·27, df=1 (p=0·07); I2=69%
Test for overall effect: Z=0·42 (p=0·68)
Events
105
77
182
Total
1286
1649
2935
Manual
94
168
262
Events
1275
2815
4090
Total
49·3%
50·7%
100·0%
Weight
Odds ratio
M–H, random, 95% CI
2013
2014
Year
1·12 (0·84–1·49)
0·77 (0·59–1·02)
0·93 (0·64–1·33)
Favours manualFavours LUCAS
00·5 0·7 1·5 2·0
Favours manualFavours LUCAS
00·5 0·7 1·5 2·0

Articles
954 www.thelancet.com Vol 385 March 14, 201
analysis provides the answer to our primary question of
the eff ectiveness of implementation of mechanical CPR
into routine clinical practice. The two CACE analyses
estimate the treatment eff ect of LUCAS in participants
who were compliant with the trial protocol, and those
where LUCAS was actually used. Since this approach
retains the initial randomised assignment, it overcomes
the issues relatedto per-protocoland on-treatment
analyses. These analyses served to confi rm the direction
of fi ndings from the intention-to-treat analysis.
The fi ndings of marginally worse neurological outcomes
and lower survival in patients presenting with an initially
shockablerhythm was unexpected.Although these
analyses were defi ned a priori, they were not the primary
objectiveof the trial and should be interpretedwith
caution and deemed as hypothesis generating. One of
these hypotheses is that interruptions in CPR during
devicedeploymentcould causereducedcardiacand
cerebral perfusion. Alternatively, slightly more patients
received adrenaline after randomisation in the LUCAS
group than in the control group, which might increase
cardiac instability and impair cerebral microcirculation.25
Finally, deployment of LUCAS before the fi rst shock is
likely to have led to a delay in the time to fi rst shock, which
might in itself reduce survival.26
We chose to use a cluster randomised design with
vehiclesas the unit of randomisation.This design
allowed us to include all cardiac arrests where a trial
vehicle was fi rst on scene, because recruitment to the
trial was not dependenton a paramedicmaking a
decision to randomise. This means that one of the major
potential drawbacks of cluster randomisation, selection
bias, was avoided because we have included in the trial
all of the eligible patients. It is possible that selection
bias could be introduced by paramedics having a lower
threshold for initiation of resuscitation, in view of the
knowledgethat a LUCAS devicewas present.The
independent data monitoring committee monitored this
throughout the trial, by looking at the proportions of
patients resuscitated when LUCAS and control vehicles
were fi rst on scene, and the characteristics of patients
recruited to the two trial groups. No evidence of diff erent
resuscitation thres holds was found.
The implementation process was tailored to refl ect
how such technology would be implemented in the
NHS and the study fi ndings should be considered in
that context. Health-care systems will need to consider
carefully the fi ndings from this and previous studies
when considering the role of mechanical CPR during
out-of-hospital cardiac arrest. Deployment across entire
services will require substantial capital investment. This
investment must be balanced against the accepted role
such devices will continue to have when manual CPR is
impractical or increased risk (eg, in a moving
ambulance).Where organisationsdecide to adopt
mechanicalCPR it seems essentialthat suffi cient
resourcesare made availableto supportinitial and
regular refresher training and ongoing quality
assurance. Future research should look to defi ne th
optimum method and frequency of such training.
In conclusion,this trial was unable to show any
superiorityof mechanicalCPR and highlights the
diffi culties of training and implementation in real world
EMS systems.
Contributors
GDP, RL, TQ, CDD, MWC, SEL, AMS, MW, RW, and SG designed the
trial. JH, AC, MS, RW, AW, HP, JB, JW, KH led recruitment and data
collection. RL analysed the data which was interpreted by the co-author
GDP, RL, TQ, CDD and SG drafted the paper with input from co-authors.
The fi nal paper has been approved by all authors.
Collaborators
Vikki Gordon, Charlotte Kaye, Sam Brace-McDonnell, Hayley Johnson,
Inga Ruders, Sonia Davis, Sarah Rumble, Kate Packard, Bev Hoddell,
Nikki Morrow, Claire Daff ern, Susie Hennings, Sarah Duggan,
Adrian Willis, Chockalingam Muthiah, Gill Price, Ian Jones,
Phil Hallam, Emma Harris, Andy Rosser, Garry Parcell, Kate Wilson,
Ed England, Ian Teague, Helen Rooke, Nicola Brock, Rebecca Jones,
Sonia Byers, Laura Blair, Gary Shaw, Graham McClelland, Julie Norris,
Katie Williams, Chris McCabe, Claire Hulme, and Charlotte Kelly.
Declaration of interests
GDP, RL, TQ, CDD, MWC, SEL, A-MS, MW, RW, and SG report grants
from NIHR HTA Programme during the conduct of the study. The other
authors declare no competing interests.
Acknowledgments
This is a summary of independent research funded by the National
Institute for Health Research’s (NIHR) Health Technology Assessment
Programme (Grant Reference Number HTA – 07/37/69). The views
expressed are those of the author(s) and not necessarily those of the NH
the NIHR, or the Department of Health. GDP is supported as a Director
of Research for the Intensive Care Foundation. We thank the independe
members of the Trial Steering Committee (Jon Nicholl, Helen Snooks,
Fionna Moore, Alasdair Gray, Martyn Box, Father Neil Bayliss, and
John Long) and the Data Monitoring Committee (Marion Campbell,
Jerry Nolan, and Kathy Rowan).
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Comment
920 www.thelancet.com Vol 385 March 14, 201
The appropriate role for mechanical chest compression
devicesin pre-hospitalcare has beendebatedin
recent years.1 The quality of manual cardiopulmonary
resuscitation(CPR) during out-of-hospitalcardiac
arrest is often less than optimum, and aff ects survival.2
Mechanicalcompressiondevicesare an attractive
alternative: they never get tired, give consistent chest
compressions,and allow CPR to continueduring
transferof the patient.Resultsfrom two studies3,4
of implementation of mechanical CPR devices in the
so-called real world showed higher rates of return of
spontaneous circulation and survival to dischar
mechanical CPR than with manual CPR. However, r
from three randomised trials5–7 did not show signifi cant
survivalbenefi tfor mechanicalCPR comparedwith
manual CPR.
In The Lancet, Gavin Perkins and colleagues8 describe
a pragmatic, cluster-randomised trial including
with non-traumatic out-of-hospital cardiac arrest
four UK ambulance services. Ambulances were ran
assigned to either mechanical CPR (with the L
device, fi gure) or manual CPR. The investigators e
Out-of-hospital cardiac arrest: manual or mech
fell in contrast to gains after most previous budgets.13
Regular, rigorous, and structured advice to governments,
especially ministries of fi nance, given by credible experts
could help to triple excise tax and raise the price of the
cheapestcigarettes.Globaleff ortshavesuccessfully
used peer interventions to change the behaviour of sex
workers;14 similar peer interventions could change the
behaviour of fi nance ministers.
Eff ectivetobaccocontrolover the next decade
requirespriorityactionsto increaseexcisetaxes,
while expandingcoverageof plain packagingand
bans on public smoking and on tobacco advertising,
sponsorship, and promotion.1,3,5 Priority should also be
given to strengthening research on tobacco use that
is locally relevant—eg, by supporting the Richard Doll
CentenaryClassicCausesConsortium—sincecountry-
specifi cdata can informpolicyand generatevital
political attention to tobacco control. Cancer Research
UK will launch a global tobacco control research plan
this year to generate new knowledge that can be used
to support tobacco control measures. Focused actions
could strengthen tobacco control worldwide and help
to implement the FCTC more eff ectively. If so, we could
bring forward the time when many tens of millions of
adult smokers quit and smoking uptake among young
people falls, preventing millions of premature deaths.
Prabhat Jha
Centre for Global Health Research, St Michael’s Hospital and Dalla
Lana School of Public Health, University of Toronto, Toronto,
ONT M5B 1W8, Canada
[e-mail]
For the Richard Doll Centenary
see https://www.ox.ac.uk/media/
global/wwwoxacuk/localsites/
gazette/documents/Richard_
Doll_Centenary_Meeting_
programme.pdf
I declare no competing interests.
1 WHO. WHO report on the global tobacco epidemic, 2013: enforcing b
on tobacco advertising, promotion and sponsorship. Geneva: World
Organization, 2013.
2 Giovino GA, Mirza SA, Samet JM, et al, for The GATS Collaborative Gr
Tobacco use in 3 billion individuals from 16 countries: an analysis of
nationally representative cross-sectional household surveys. Lancet
380: 668–79.
3 Jha P, Peto R. Global eff ects of smoking, of quitting, and of taxing to
N Engl J Med 2014; 370: 60–68.
4 Smith M, Zhou M, Wang L, Peto R, Yang G, Chen Z. Peak fl ow as a p
of cause-specifi c mortality in China: results from a 15-year prospect
study of ~170,000 men. Int J Epidemiol 2013; 42: 803–15.
5 Jha P, MacLennan M, Yurekli A, et al. Global tobacco control. In:
Gelband H, Jha P, Sankarnaryanan R, Horton S, eds. Cancer-disease
priorities 3rd edition. New York: World Bank and Oxford University P
(in press).
6 Jha P. Avoidable global cancer deaths and total deaths from smoking
Nat Rev Cancer 2009; 9: 655–64.
7 Cancer Research UK. Plain packaging campaign. Setting the standar
plain cigarette packaging. 2015. http://www.cancerresearchuk.org/
support-us/campaign-for-us/setting-the-standard-for-plain-cigarette-
packaging (accessed March 3, 2015).
8 Sitas F, Egger S, Bradshaw D, et al. Diff erences among the coloured
black and other South African populations in smoking-attributed mo
at ages 35–74 years: case-control study of 481 640 deaths. Lancet 2
382: 685–93.
9 Alam DS, Jha P, Ramasundarahettige C, et al. Smoking-attributable m
in Bangladesh: proportional mortality study. Bull World Health Organ
91: 757–64.
10 International Agency for Research on Cancer. Eff ectiveness of tax a
policies for tobacco control. Lyon: International Agency for Research
Cancer and WHO, 2011.
11 WHO. WHO technical manual on tobacco tax administration. Geneva
World Health Organization, 2010.
12 Gilmore AB, Fooks G, Drope J, Aguinaga Bialous S, Jackson RR. Expos
and addressing tobacco industry conduct in low-income and middle-
income countries. Lancet 2015; 385: 1029–43.
13 Mukherjee W. Budget 2015: cigarette prices to go up by 10–15%.
Economic Times of India Feb 28, 2015.
14 Arora P, Nagelkerke NJ, Moineddin R, Bhattacharya M, Jha P. Female
work interventions and changes in HIV and syphilis infection risks fro
2003 to 2008 in India: a repeated cross-sectional study. BMJ Open 2
3: e002724.
Published Online
November 16, 2014
http://dx.doi.org/10.1016/
S0140-6736(14)61941-3
See Articles page 947

Comment
www.thelancet.com Vol 385 March 14, 2015 921
4471 patients (1652 patients in the LUCAS-2 group,
and 2819patientsin the controlgroup).However,
only 985 (60%) patients in the mechanical CPR group
actuallyreceivedthe LUCAS-2intervention,as did
11 (<1%) in the control group. 30 day survival (analysed
by intention to treat) was similar for mechanical CPR
(104 [6%] of 1652 patients) and manual CPR (193 [7%]
of 2819 patients; adjusted OR 0·86, 95% CI 0·64–1·15).
Neurologicalsurvivalwith favourableneurological
outcome at 3 months was lower in the mechanical CPR
group than in the manual CPR group (adjusted OR 0·72,
95% CI 0·52–0·99).
The authors should be commended for attempting
a real-worldclinicaltrial on an importantissuefor
Emergency Medical Services (EMS) systems worldwide.
This studyportraysthe complexitiesand diffi culties
surroundinglarge-scaleresuscitationtrials,and the
importanceof attentionto implementationand
trainingin the assessmentof any new technology.
The somewhat low device usage rate (60%) reported
in this studywas due to diffi cultiesin deviceuse
(15%),unknownreasons(6%),and non-compliance
(16%).Even with apparentcompliance,whether
operationalissuesresultedin implementationdelays
with the mechanical device is unknown. The absence of
diff erence (or even inferiority) in outcomes in the trial
group might not be due to the treatment or device itself,
but to attention to training, compliance to protocols,
and implementation.
When implementing a programme with a mechanical
device that has weight and bulk, we cannot presume
thatambulancecrews wouldalwayscarry the device
with them when attending to a call. It would be relevant
to know whether the LUCAS device was immediately
started at the site or later, including in the ambulance. If
later, substantial time delays in initiating mechanical CPR
might have negated potential for benefi t in device use.
The time from emergencycall to arrivalof the
vehicle or ambulance crew at the patient’s side, as an
indicatorof durationof collapsebeforeintervention
by ambulancecrew,might underestimatecollapse
intervals. This study8 did not calculate collapse time or
collapse duration before application of interventions.
Conventional therapies for cardiac arrest seem to have
minimumeff ectafterlong collapseintervals.Long
intervals in the intervention group might conceal the
eff ect of these interventions. Assessment of the eff ect
of this collapse interval on outcomes after mechanical
CPR might throw light on the relative usefulness of this
mode of resuscitation.
About 60% of cardiacarrestsattendedwere
deemednot eligibleand had no resuscitation
attempted (6482 of 11 171). This proportion is rather
high comparedwith that in many EMS systems
internationally. This fi nding raises questions of selective
resuscitation by ambulance crews, although the study
team didmonitorfor enrolmentbiasandnotedno
diff erence between study groups.
Quality of implementation is an especially important
issue with regard to the benefi t or harm of mechanical
CPR. Interruptions to CPR and delays in application of
mechanical CPR devices are major factors that aff ect
outcomes.9 Wang and colleagues showed that human
error and lack of training with mechanical CPR led to
prolonged intervals without chest compression.10
Attention to team training and focusing on quality
of deployment of mechanical CPR devices alone can
greatlyimproveoutcomes.11 The absenceof quality
implementationmeasuresin this study,8 such as
dataon delaysin applicationof the deviceor CPR
interruptions, makes it diffi cult to refute the hypothesis
that the outcomes noted are possibly more an eff ect of
the quality of implementation rather than the therapy
in question.
Although this study does not give us a defi nitive
answer to the debate between manual and mechanical
CPR,it doesthrowa spotlighton implementation
Figure: LUCAS-2 mechanical chest compression device
Marcus Eng Hock Ong

Comment
922 www.thelancet.com Vol 385 March 14, 201
Non-alcoholic steatohepatitis occurs when hepatic fat,
infl ammation, and liver-cell injury develop in insulin-
resistantindividuals.Reportsfrom US transplant
registriesshow that non-alcoholicsteatohepatitis
is the third leading cause of end-stage liver disease,1
and the second most common cause of primary liver
cancerin patientslistedfor liver transplantation.2
Yet no pharmacologicaltherapyfor non-alcoholic
steatohepatitis is approved.
In The Lancet,Brent Neuschwander-Tetriand
colleagues3 report on the eff ects of obeticholic acid,
a synthetic farnesoid X receptor agonist, in patients
with non-alcoholicsteatohepatitis,in a placebo-
controlled,randomisedtrial (FLINT).Patientswere
treated for 72 weeks and the primary endpoint was
improvementin histology,as measuredby a two-
point reductionin a compositeactivityhistological
score without worsening of fi brosis. The therap
phase of the trial was stopped early partly be
preplanned interim analysis showed that more pat
on obeticholic acid (50 [45%] of 110) than on place
(23 [21%]of 109) reachedthe primaryendpoint
(relative risk 1·9, 95% CI 1·3–2·8). Unexpected
a trial not poweredto detectfi broticchanges,the
authorsalso reportedan improvementin fi brosis:
36 (35%)of 102 obeticholicacid-treatedpatients
regressed by one stage or more versus 19 (19
98 placebo-treatedpatients.Neitherpioglitazone,a
peroxisome proliferator-activated receptor-γ ago
nor vitaminE signifi cantlyimprovedfi brosisafter
2 years of treatment, despite similar reductions in
alcoholicfattyliverdisease(NAFLD)activityscore.4
Starting the battle to control non-alcoholic stea
and quality. EMS services should aim to provide the
best qualityof CPR possible.High-qualitymanual
CPR requiresEMS commitmentto trainingand
qualityreview.MechanicalCPR requiresthe same
commitment to training and attention to deployment
practices.MechanicalCPR is also morecostlythan
manualCPR. EMS systemsworldwideroutinely
transport patients with cardiac arrest to hospital with
ongoingmanualCPR of doubtfulquality.12 Safety
concerns for unrestrained crew using manual CPR in
a moving ambulance are real. Mechanical CPR allows
crews to be safely belted up and is a logical choice from
the safety perspective.13
*Marcus Eng Hock Ong, Venkataraman Anantharaman
Department of Emergency Medicine, Singapore General Hospital,
169608 Singapore (MEHO, VA); and Health Services and Systems
Research, Duke-NUS Graduate Medical School, 169857 Singapore
(MEHO)
[e-mail]
MEHO is principal investigator of an industry-funded study involving a mechanical
CPR device; has received grants from Laerdal Medical, grants and personal fees
from Zoll Medical Corporation, and non-fi nancial support from Bard Medical and
Zoll Medical Corporation; and has a patent method of predicting patient survival
licensed to Zoll Medical Corporation, and a patent system and method of
determining a risk score for triage pending. VA is principal investigator in an
industry-funded study on use of a mechanical CPR device in the out-of-hospital
situation; has received non-fi nancial support from Physio-Control Inc; and is a
member of the Medical Advisory Board of Falck Foundation.
Copyright © Ong et al. Open Access article distributed under the terms of CC BY.
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manual CPR during out-of-hospital cardiac arrest and ambulance tra
a systematic review. Scand J Trauma Resusc Emerg Med 2012; 20: 3
2 Wik L, Kramer-Johansen J, Myklebust H, et al. Quality of cardiopulmo
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rate of return of spontaneous circulation in out-of-hospital cardiac ar
Prehosp Emerg Care 2005; 9: 61–67.
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load-distributing band chest compression device for out-of-hospital
cardiac arrest resuscitation. JAMA 2006; 295: 2629–37.
5 Hallstrom A, Rea TD, Sayre MR, et al. Manual chest compression vs u
an automated chest compression device during resuscitation followi
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department. Resuscitation 2013; 84: 508–14.
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cardiopulmonary resuscitation. Prehosp Emerg Care 2011; 15: 106.
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cardiopulmonary resuscitation in basic life support systems.
Prehosp Emerg Care 2013; 17: 491–500.
Published Online
November 7, 2014
http://dx.doi.org/10.1016/
S0140-6736(14)62010-9
See Articles page 956
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