Advanced Airway Placement

Advanced airway placement (ETT vs SGA)
Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does tracheal tube insertion as first advanced
airway (I), compared with insertion of a supraglottic airway as first advanced airway (C), change ROSC,
CPR parameters, development of aspiration pneumonia, Survival with Favorable neurological/functional
outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days,
60 days, 180 days AND/OR 1 year (O)?
The information provided is currently in DRAFT format and is NOT a FINAL version
Consensus on Science:
EGTA (I) versus tracheal intubation (C) For the critical outcome of survival to hospital discharge we have
identified very low quality evidence (downgraded for very serious concerns about risk of bias and
imprecision) from one RCT enrolling 175 OHCAs show no difference between EGTA and tracheal
intubation (OR 1.19 95% CI 0.5 - 3.0) [Goldenberg 1986 90] Combitube (I) versus tracheal intubation
(C) For the critical outcome of survival to hospital discharge we have identified very low quality evidence
(downgraded for very serious concerns about risk of bias and imprecision) from one RCT enrolling 173
OHCAs that showed no difference between Combitube and tracheal intubation (OR 2.38 95% CI 0.5
12.1) [Rabitsch 2003 27] and very low quality evidence from one observational study of 5822 OHCAs
that showed no difference between tracheal intubation by paramedics and Combitube insertion by
emergency medical technicians (EMTs) (adjusted OR 1.02; 95% CI 0.79 -1.30) [Cady 2009 495]. For the
important outcome of ROSC we have identified very low quality evidence from one observational study of
5822 OHCAs that showed no difference between tracheal intubation by paramedics and Combitube
insertion by emergency medical technicians (EMTs) (adjusted OR 0.93; 95% CI 0.82 -1.05). [Cady 2009
495]. LMA (I) versus tracheal intubation (C) For the critical outcome of survival to hospital discharge we
have identified very low quality evidence from one observational study of 641 OHCAs that showed lower
rates of survival to hospital discharge with insertion of an LMA compared with tracheal tube (OR 0.69;
95% CI 0.4 1.3) [Shin 2012 313]. Supraglottic airways (SGAs: Combitube, LMA, laryngeal tube)
versus tracheal intubation For the critical outcome of favourable neurological survival we have identified
low quality evidence from one observational study of 5377 OHCAs showing no difference between
tracheal intubation and insertion of a SGA (adjusted OR 0.71; 95% CI 0.39 1.30) [Kajino 2011 R236],
from one observational study of 281,522 OHCAs showing higher rates of favourable neurological
outcome between insertion of a SGA and tracheal intubation (OR 1.11; 95% CI 1.0 1.2) [Hasegawa
2013 257] and from two studies showing higher rates of favourable neurological outcome between
tracheal intubation and insertion of a SGA (8701 OHCAs adjusted OR 1.44; 95% CI 1.10 1.88
[McMullan 2014 617]) and (10,455 OHCAs adjusted OR 1.40; 95% CI 1.04 1.89 [Wang 2012 1061]).
Supraglottic airways (SGAs: Combitube and LMA) versus tracheal intubation For the important outcome
of ROSC we have identified very low quality evidence from one observational study of 713 OHCAs that
showed no difference between tracheal intubation and Combitube or LMA insertion by EMTs or
emergency life-saving technicians (ELTs) (OR 0.65; 95% CI 0.4 1.2). [Yanagawa 2010 340].
Supraglottic airways (SGAs: Esophageal obturator airway and LMA) versus tracheal intubation For the
critical outcome of neurologically favourable one-month survival we have identified very low quality
evidence from one observational study of 138,248 OHCAs that showed higher rates of neurologically
favourable one-month survival with tracheal intubation compared with insertion of an esophageal
obturator airway or LMA (OR 0.89; 95% CI 0.8 1.0). [Tanabe 2013 389] For the critical outcome of
one-year survival we have identified very low quality evidence from one observational study of 923
OHCAs that showed no difference in one-year survival with tracheal intubation compared with insertion
of an esophageal obturator airway or LMA (OR 0.89; 95% CI 0.3 2.6). [Takei 2010 715]. For the
critical outcome of one-month survival we have identified very low quality evidence from one observation
study that showed no difference in one-month survival between tracheal intubation and insertion of an
esophageal obturator airway of an LMA (OR 0.75; 95% CI 0.3 1.9) [Takei 2010 715] and very low
quality evidence from another observation study that showed higher one-month survival with tracheal
intubation compared with insertion of an esophageal obturator airway of an LMA (OR 1.03; 95% CI 0.9
1.1) [Tanabe 2013 389] For the important outcome of ROSC we have identified very low quality evidence
from one observational study of 923 OHCAs that showed a higher rate of ROSC with tracheal intubation
compared with insertion of an esophageal obturator airway or LMA (OR 0.71; 95% CI 0.4 1.2). [Takei
2010 715].
Treatment Recommendation:
We suggest using either a supraglottic airway or tracheal tube as the initial advanced airway
management during CPR (weak recommendation, very low quality evidence) for out of hospital cardiac
arrest. We suggest using either a supraglottic airway or tracheal tube as the initial advanced airway
management during CPR (weak recommendation, very low quality evidence) for in hospital cardiac
arrest.
CoSTR Attachments:
ALS 714 Evidence Profile for SGA versus TT_Part 2_JN_EL_21Dec14.docx
ILCOR Slides ALS 714 SGA VS TT Dallas 2015.ppt
ALS 714 CoS and TR for SGA versus TT_JN_EL_PM_21Dec14.docx
ALS 714 Summary of Bias Assessments for SGA versus TT5.xlsx
Airway placement (Basic vs Advanced)

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does insertion of an advanced airway (ETT or
supraglottic airway) (I), compared with basic airway (bag mask +/- oropharyngeal airway) (C), change
Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days
AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC, CPR
parameters, development of aspiration pneumonia (O)?
All advanced airways (I) versus bag-mask (C) For the critical outcome of favourable neurological survival
at one month we have identified very low quality evidence (downgraded for very serious concerns about
risk of bias and indirectness, and serious concerns about inconsistency) from one observational study of
648549 OHCAs showing a lower unadjusted rate of survival with insertion of an advanced airway
(tracheal tube, LMA, LT or Combitube) compared with management with a bag-mask (1.1% vs 2.9%;
odds ratio [OR], 0.38; 95% CI, 0.36-0.39)) [Hasegawa 2013 257]. When adjusted for all known
variables the odds ratio was 0.32 (0.30-0.33). For the critical outcome of favourable neurological
survival to hospital discharge we have identified very low quality evidence (downgraded for very serious
concerns about risk of bias and indirectness, and serious concerns about inconsistency) from one
observational study of 10691 OHCAs showing a lower unadjusted rate of survival with insertion of an
advanced airway (tracheal tube, LMA, LT or Combitube) compared with management with a bag-mask
(5.3% vs 18.6%; odds ratio [OR], 0.25; 95% CI, 0.2 0.3)) [McMullan 2014 617]. In an analysis of
3398 propensity-matched patients from the same study, the odds ratio for favourable neurological
survival at hospital discharge (bag-mask versus advanced airway) adjusted for all variables was 4.19
(3.09 5.70). Tracheal intubation (I) versus bag-mask (C) For the critical outcome of favourable
neurological survival at one month we have identified very low quality evidence (downgraded for very
serious concerns about risk of bias and indirectness, and serious concerns about inconsistency) from one
observational study of 409809 OHCAs showing a lower unadjusted rate of survival with tracheal
intubation compared with management with a bag-mask (1.0% vs 2.9%; OR 0.35 (0.31-0.38))
[Hasegawa 2013 257]. In an analysis of 357228 propensity-matched patients from the same study, the
odds ratio for favourable neurological survival at one month (tracheal intubation versus bag-mask)
adjusted for all variables was 0.42 (0.34 0.53). For the critical outcome of favourable neurological
survival to hospital discharge we have identified very low quality evidence (downgraded for very serious
concerns about risk of bias and indirectness, and serious concerns about inconsistency) from one
observational study of 7520 OHCAs showing a lower unadjusted rate of survival with tracheal intubation
compared with management with a bag-mask (5.4% vs 18.6%; odds ratio [OR], 0.25; 95% CI, 0.2
0.3)) [McMullan 2014 617]. Supraglottic airways (I) versus bag-mask (C) For the critical outcome of
favourable neurological survival at one month we have identified very low quality evidence (downgraded
for very serious concerns about risk of bias and indirectness, and serious concerns about inconsistency)
from one observational study of 607387 OHCAs showing a lower unadjusted rate of survival with
insertion of a supraglottic airway (LMA, LT or Combitube) compared with management with a bag-mask
(1.1% vs 2.9%; OR 0.38 (0.37-0.40)) [Hasegawa 2013]. In an analysis of 357228 propensity-matched
patients from the same study, the odds ratio for favourable neurological survival at one month
(supraglottic airway versus bag-mask) adjusted for all variables was 0.36 (0.33-0.40).
We suggest using either an advanced airway or a bag mask for airway management during CPR (weak
recommendation, very low quality evidence) for out of hospital cardiac arrest. We suggest using either
an advanced airway or a bag mask for airway management during CPR (weak recommendation, very low
quality evidence) for in hospital cardiac arrest.
CoSTR Attachments:
ALS 783 Evidence Profile SGA versus Basic_10Jan15.docx
Summary of Bias Assessments for Basic versus Advanced 14Dec14.xlsx
ALS 783 CoS and TR for basic versus advanced 10Jan15.docx
ALS 783 Evidence Profile Tracheal intubation versus basic_10Jan15.docx
ILCOR Slides ALS 783 Advanced versus basic Dallas 2015.ppt
ALS 783 Evidence profile any advanced airway versus Basic_10Jan15.docx
Antiarrhythmic drugs for cardiac arrest

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does antiarrhythmic drugs (e.g. lidocaine,
amiodarone, other) administration (I), compared with not using antiarrhythmic drugs (no drug or
placebo) (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60
days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year,
ROSC (O)?
Amiodarone (I) versus no amiodarone (C) For the important outcome of ROSC, we have identified one
RCT (GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of (or developing) VF
or pulseless VT refractory to 3 shocks showing an improved rate of ROSC with administration of
amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (64% vs 41%; p=0.03)
[Kundenchuk 1999]. For the critical outcome of survival at discharge, we have identified one RCT
(GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of (or developing) VF or
pulseless VT refractory to 3 shocks showing a similar rate of survival with administration of amiodarone
(300 mg after 1 mg of adrenaline) compared with no drug (13.4% vs 13.2%; p=ns) [Kundenchuk 1999].
For the critical outcome of survival with favorable neurological/functional outcome at discharge, we have
identified one RCT (GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of (or
developing) VF or pulseless VT refractory to 3 shocks showing a similar rate of survival with favorable
neurological outcome with administration of amiodarone (300 mg after 1 mg of adrenaline) compared
with no drug (53% vs 50% of survivors; p=ns) [Kundenchuk 1999]. Lidocaine (I) versus no lidocaine (C)
For the important outcome of ROSC, we identified 2 retrospective observational single center studies
(GRADE: very low; very serious risk of bias) with conflicting results: - Herlitz [1997] et al. showed in 290
patients who suffered from OHCA with VF refractory to 3 shocks an improved rate of ROSC with
administration of lidocaine (50 mg, repeatable up to 200 mg) compared with no drug (45% vs 23%; p
There are no studies that show improved survival to hospital discharge or functional survival with the use
of antiarrhythmics in cardiac arrest patients refractory to VF/pVT. - We suggest the use of amiodarone in
adult patients who suffer OHCA with refractory VF/pVT to improve rates of ROSC (Weak
recommendation; high confidence in effect estimate). - Clinicians might consider lidocaine or nifekalant
for in adult patients who suffer OHCA and IHCA , respectively (Weak recommendation, very low
confidence in effect estimates). - We suggest against the use of magnesium in adult patients who are in
OHCA in any rhythm (Strong recommendation, moderate confidence in effect estimate).
CoSTR Attachments:
ALS 428 should-lidocaine-vs-no-lidocaine-be-used-for-adults-who-are-in-cardiac-arrest-in-anysetting.pdf
ALS 428 should-nifekalant-vs-no-nifekalant-be-used-for-adults-who-are-in-cardiac-arrest-in-anysetting.pdf
ALS 428 should-magnesium-vs-no-magnesium-be-used-for-adults-who-are-in-cardiac-arrest-in-anysetting.pdf
ALS 428 should-amiodarone-vs-placebo-be-used-for-adults-who-are-in-cardiac-arrest-in-anysetting.pdf
Antiarrhythmic drugs post resuscitation

Question Type:
Intervention
Full Question:
Among adults who are experiencing ROSC after cardiac arrest in any setting (P), does prophylactic
antiarrhythmic drugs given immediately after ROSC (I), compared with no use of antiarrhythmic drugs
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180
days AND/OR 1 year, development of cardiac arrest, Survival only at discharge, 30 days, 60 days, 180
days AND/OR 1 year, recurrence of VF, incidence of arrhythmias (O)?
Proposed Consensus on Science statements B-blockers (I) versus no b-blockers (C) For the critical
outcome of survival at 6 months we have identified low quality evidence from one observational study of
98 patients resuscitated from OHCA showing a higher unadjusted rate of survival with administration of
b-blockers (metoprolol or bisoprolol) for 72 hours post-ROSC compared with no drug (65.8% vs 21.1%;
p< 0.0001). In an unadjusted analysis on 1721 patients the rate of recurrence of VF was also lower
(16.7% vs 37.4%, p< 0.0001), as it was in an adjusted analysis (OR 1.49, 1.151.95 95% CI)
[Kudenchuk 2013]. 1692 papers have been considered from which 39 from fulfilled the search. After
reviewing them, there is no convincing evidence that the routine use of magnesium, amiodarone,
lidocaine, procainamide, bretylium and nifekalant after ROSC in human CPR increased survival to
hospital discharge. Antiarrhythmic drugs may improve immediate recovery from cardiac arrest
(especially those related to ventricular tachyarrhythmias) but fail to assure survival thereafter. Lidocaine,
procainamide and bretylium have been extensively reviewed in previous issues of CoSTR (1005-2010)
showing no important effects and will not be considered in this report. From all the remaining
antiarrhythmic drugs, the one with best results seem to be amiodarone. Newer drugs, like nifekalant,
have not been extensively tested in humans although some observations, non-randomized trials and
animal studies show promising results when compared with amiodarone. Thus the last mentioned drug is
still the best available one to be considered for arrhythmias involved in cardiac arrest in the early stages
(arrival to the hospital from OHCA) although no changes have been registered in survival after hospital
discharge.
We are making no recommendation with regards to the routine prophylactic use of antiarrhythmic drugs
post-ROSC in all OHCA patients (GRADE used for evidence evaluation and synthesis only - very low
confidence in effect estimate). Clinicians might consider either lidocaine or b-blockers in post-ROSC
patients who had VT/VF as their initial rhythm (Weak recommendation, very low confidence in effect
estimate).
CoSTR Attachments:
ALS493 Antiarrhythmics Post ROSC 20150110_.pptx
CoSTR Statement - ALS 493 Antiarrhythmic drugs post resuscitation 20150110.docx
Pellis - Grade Table.docx
Cardiac arrest during PCI

Question Type:
Intervention
Full Question:
Among adults who have a cardiac arrest in the cardiac cathether laboratory (P), does any special
intervention or change in care (e.g. catheterization during CPR, cardiopulmonary bypass, balloon pump,
different timing of shocks) (I), compared with standard resuscitation care (e.g. CPR, drugs and shocks
according to 2010 treatment algorithm) (C), change Survival with Favorable neurological/functional
60 days, 180 days AND/OR 1 year, ROSC (O)?
There were no comparative studies evaluating the survival benefit of mechanical CPR, Individual
noncomparative case series reported variable survival rates. For the outcomes of survival with
favourable neurological/functional outcome at discharge, 30 days, 60 days, 90 days, 180 days, and 1
year we identified no papers. For the outcomes of survival at 30 days, 60 days, 90 days, and 180
days we identified no papers. For the outcomes of ROSC, survival at discharge and 1-year survival we
identified 1 very low quality evidence (downgraded for risk of bias and imprecision) observational study
that compared ECMO vs. IABP in a total of 21 patients. The study showed improved rates of ROSC 9 of
13 (69.23%) vs. 1 of 8 (12.5%), improved survival to discharge 8 of 13 (61.5%) compared with 0 of 8
(0%), and increased 1-year survival 7 of 13 (53.85%) compared to 0 of 8 (0%) for ECMO compared to
IABP in patients who have a cardiac arrest in the cardiac catheterization laboratory. Individual noncomparative case series of ECMO also observed a high rate of survival.
We suggest using ECLS (cardiopulmonary bypass) as a rescue treatment when initial therapy is failing
for cardiac arrest that occurs during percutaneous coronary interventions (weak recommendation, very
low quality evidence). We are making no recommendations with regard to the routine use of mechanical
CPR in this setting (GRADE has no data).
CoSTR Attachments:
PCI_CA - Dallas 2015.pptx
2015 ALS PCI CoSTR StatementDraft.docx
Bias and Data copy5.xlsx
eCPR vs manual CPR

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting
(P), does the use of extracorporeal CPR techniques (eCPR)(including ECMO or cardiopulmonary bypass)
(I), compared with manual CPR or mechanical CPR
(C), change survival to 180 days with good neurological outcome, survival with favorable neurologic
outcome, survival to hospital discharge with good neurological outcome, survival to hospital discharge,
ROSC (O)?
For the critical outcome of neurological outcome at 90 days after OHCA we have identified very low
quality evidence from one non-RCT enrolling 39 patients showing no benefit (OR 0.22 95% CI 0.041.20). For the critical outcome of neurological outcome at 180 days after OHCA we have identified low
quality evidence from one non-RCT enrolling 359 patients showing benefit (OR 0.22 95% CI 0.09-0.61).
For the critical outcome of neurological outcome at hospital discharge after IHCA we have identified
very low quality evidence from 3 non-RCTs enrolling 410 patients showing benefit (OR 0.42 95% CI
0.24-0.72). For the critical outcome of neurological outcome at one year after IHCA we have identified
low quality evidence from 2 non-RCTs enrolling 199 patients showing no benefit (OR 0.54 95% CI 0.241.23).
We suggest using eCPR for OHCA (weak recommendation, low quality of evidence). We suggest using
eCPR for IHCA (weak recommendation, low quality of evidence).
_______________________________________________________________________________ We
suggest using eCPR for select* populations of OHCA (weak recommendation, low quality of evidence).
We suggest using eCPR for select* populations of IHCA (weak recommendation, low quality of evidence).
*In making these recommendations we note that the published series used rigorous inclusion criteria to
select patients for eCPR, and that our recommendation should apply to similar populations.
CoSTR Attachments:
eCPRvsManualCPR_Summary.docx
eCPR_ILCORSlideDec2014.pptx
eCPRvsManualCPR_SOF.docx
ETCO2 to predict outcome of cardiac arrest

Question Type:
Prognostic
Full Question:
Among adults who are in cardiac arrest in any setting (P), does any end-tidal CO2 level value, when
present (I), compared with any end-tidal CO2 level below that value (C), change (O)?
For the important outcome of ROSC we have identified low quality evidence from 3 observational
studies enrolling 302 patients (Ahrens 2001, 391; Callaham 1990, 358; Cantineau 1996, 791) showing a
correlation with Initial ETCO2 10 mmHg when compared to < 10 mmHg (OR 10.7 95% CI 5.6 20.3).
For the important outcome of ROSC we have identified low quality evidence from 3 observational
studies enrolling 367 patients (Ahrens 2001, 391; Levine 1997, 301; Wayne 1995, 762) showing
correlation with 20 min ETCO2 10 mmHg when compared to < 10 mmHg (OR 181.6 95% CI 40.1
822.6). For the critical outcome of survival at discharge we have identified low quality evidence from 1
observational study enrolling 127 patients (Ahrens 2001, 391) showing a correlation with Initial ETCO2
10 mmHg when compared to < 10 mmHg (OR 11.4 95% CI 1.4 90.2). For the critical outcome of
survival at discharge we have identified low quality evidence from 1 observational study enrolling 127
patients (Ahrens 2001, 391) showing a correlation with 20 min ETCO2 20 mmHg when compared to <
20 mmHg (OR 20.0 95% CI 2.0 203.3). We did not identify any evidence to address the critical
outcome of neurologically intact survival.
We suggest that ETCO2 10 mmHg, measured after the intubation or at 20 min of resuscitation, may be
a predictor of ROSC (weak recommendation, low quality of evidence). We suggest that ETCO2 10
mmHg, measured after the intubation, or ETCO2 20 mmHg, measured at 20 min of resuscitation, may
be a predictor of survival at discharge (weak recommendation, low quality of evidence). Although certain
ETCO2 cutoff values appear to be a strong predictor of ROSC and mortality, their utility in accurately
predict outcome during CPR is not established. Thus, we recommend against using ETCO2 cutoff values
alone as a mortality predictor or on the decision to stop the resuscitation attempt (weak
recommendation, low quality of evidence).
CoSTR Attachments:
CoS and TR ETCO2.docx
ILCOR Dallas 2015 ETCO2.pptx
SOF Table ETCO2.docx
Exhaled CO2 detection and esophageal detection devices

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest, needing/with an advanced airway, in any setting (P), does use
of devices (e.g. 1. Waveform Capnography, 2. CO2 Detection Device, 3. Esophageal detector device, or
4. Tracheal ultrasound) (I), compared with not using devices (C), change placement of the ET tube
between the vocal cords and the carina, success of intubation (O)?
For the critical outcome of confirming placement of the endotracheal tube between the cords and the
carina we have identified low grade evidence to support the use of waveform capnography.
Our treatment recommendations are unchanged from 2010 guidance. Waveform capnography is
recommended to confirm and continuously monitor the position of a tracheal tube in victims of cardiac
arrest. It should be used in addition to clinical assessment - auscultation and direct visualization are
suggested (strong recommendation based on very low quality evidence). If waveform capnography is not
available, the use of a non-waveform carbon dioxide detector or esophageal detector device in addition
to clinical assessment (auscultation and direct visualization are suggested) is an alternative.
CoSTR Attachments:
ALS ETT PICO 469.docx
Fever after cardiac arrest

Question Type:
Intervention
Full Question:
Adults with ROSC after cardiac arrest in any setting (P), does Prevention of fever to maintain strict
normothermia (I), compared with No fever control (C), change Survival with Favorable
neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only
at discharge, 30 days, 60 days, 180 days AND/OR 1 year (O)?
No interventional or observational studies were identified addressing whether fever prevention (or
treatment) after cardiac arrest improves outcome. Fever after ROSC: For the critical outcomes of
survival with good neurologic/functional outcome and/or survival only, we found very low quality
evidence from 5 observational studies (downgraded for risk of bias and indirectness) that fever after
ROSC is associated with poor outcome when TTM is not used [Zeiner 2001 2007, Langhelle 2003 247,
Nolan 2007 1207, Suffoletto 2009 1365, Gebhardt 2013 1062]. Fever after TTM: For the critical
outcomes of survival with good neurologic/functional outcome and/or survival only, we found very low
quality evidence from 6 observational studies (n =856) (downgraded for risk of bias and indirectness)
that fever after TTM is not associated with outcome [Aldhoon 2012 E68, Benz-Woerner 2012 338,
Bouwes 2012 996, Gebhardt 2013 1062, Leary 2013 1056, Cocchi 2014 365] For the same critical
outcomes we also found very low quality evidence from 2 observational studies (n = 411) (downgraded
for risk of bias, inconsistency and indirectness) that fever after TTM is associated with poor outcome
[Bro-Jeppesen 2013 1734, Winters 2013 1245]
We suggest prevention and treatment of fever in persistently comatose adults after completion of
targeted temperature management between 32 and 36 degrees Celsius (weak recommendation, very
low quality evidence)
CoSTR Attachments:
ALS 879. Fever after CA PICO. Rapid fire presentation. Dallas 2015.pptx
ALS 879. Fever after CA PICO. Full Presentation. Dallas 2015.pptx
Glucose control following resuscitation

Question Type:
Intervention
Full Question:
Among adults with ROSC after cardiac arrest in any setting (P), does a specific target range for blood
glucose management (eg. strict 4-6 mmol/L) (I), compared with any other target range (C), change
AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year (O)?
For the critical outcome of survival to hospital discharge, one RCT of 90 subjects, downgraded for risk of
bias, found no reduction in 30-day mortality (RR 0.94; 95%CI 0.53-1.68) when subjects were assigned
to strict (4-6mmol/L) versus moderate (6-8 mmol/L) glucose control (Oksanen 2007). For the critical
outcome of survival to hospital discharge, one before-and-after observational study of 119 subjects
found reduced in-hospital mortality (RR 0.46; 95%CI 0.28-0.76) after implementation of a bundle of
care that included defined glucose management (5-8 mmil/L), but the isolated effect of glucose
management is confounded by and cannot be separated from the effect of other parts of the bundle
(Sunde 2007).
We suggest not selecting any specific target range of glucose management versus any other target
range in adults with ROSC after cardiac arrest (weak recommendation, moderate quality of evidence). In
making this recommendation, we noted that strict glycemic control is labor intensive. In other
populations, implementation of strict glycemic control is associated with increased episode of
hypoglycemia, which might be detrimental. There are no data that the approach to glucose management
chosen for other critical care populations should be modified for the cardiac arrest population.
CoSTR Attachments:
SummarofBiasAssessmentsGlucose.xlsx
GlucosePICO_draft2.docx
ILCOR Data Collection Form Glucose jz.xls
GlucosePICO_slides.ppt
SOFtable.tiff
GRADEtable.tiff
Hemodynamic support post resuscitation

Question Type:
Intervention
Full Question:
Among adults with ROSC after cardiac arrest in any setting (P), does titration of therapy to achieve a
specific hemodynamic goal goal (e.g. mean arterial pressure > 65 mmHg) (I), compared with no
hemodynamic goal (C), change Survival with Favorable neurological/functional outcome at discharge, 30
days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR
1 year (O)?
There are no RCTs addressing hemodynamic goals post resuscitation. 1. Titration of therapy to achieve a
specific hemodynamic goal (e.g. mean arterial pressure > 65 mmHg) compared to no hemodynamic goal
For the critical outcome of survival with favorable neurological/functional outcome we have identified
very low quality evidence (downgraded for risks of bias and publication bias) from one multicentre
retrospective non-intervention study including 8736 subjects that found post return of spontaneous
circulation (ROSC) systolic blood pressure (SBP) 80 mm Hg showed no difference in mortality or
neurological outcome at hospital discharge (Gaieski 2009, 418). One prospective observational study of
118 patients using historical controls and a aiming for MAP >65 mm Hg showed survival to hospital
discharge with a favourable neurological outcome in 34/61 (56%) up to one year, versus 15/58 (26%) in
the control period (OR 3.61, CI 1.66-7.84, p=0.001) (Sunde 2007, 29). One cohort study of 148 patients
when a MAP 100 mm Hg or < 100 mm Hg after ROSC. Good neurological recovery was independently
and directly related to MAP measured during 2 hours after ROSC (rs=.26; P 65 mmHg within 6 hours,
resulted in an in-hospital mortality of 55.2% (bundle) vs. 69.2% (prebundle) (P = 0.29). Bundle patients
achieved good neurologic outcome compared patients, CPC 1 or 2 in 31 vs. 12% patients, respectively (P
= 0.08) (Walters 2011, 360). One prospective single centre observational study assessed the association
between increasing time-weighted average mean arterial pressures and good neurologic outcome.
Among 151 patients receiving a bundle of therapies, 44 (29%) experienced good neurologic outcome
and a time-weighted average MAP threshold > 70 mm Hg had the strongest association with good
neurologic outcome (odds ratio, 4.11; 95% CI, 1.3412.66; p = 0.014) (Kilgannon 2014, 2083). One
retrospective study of bundle therapy targeting a MAP >80 mm Hg in 168 patients showed survivors had
higher MAPs at 1 h (96vs. 84 mmHg, p\0.0001), 6 h (96 vs. 90 mmHg, p = 0.014), and 24 h (86 vs. 78
mmHg, p = 0.15) than non-survivors. Increased requirement for vasoactive agents was associated with
mortality at all time points. Among those requiring vasoactive agents, survivors had higher MAPs than
non-survivors at 1 h (97 vs. 82 mmHg, p =\0.0001) and 6 h (94 vs 87 mmHg, p = 0.05) (Beylin 2013,
1982). For the critical outcome of survival we have identified very low quality evidence (downgraded for
risks of bias and publication bias) from two studies including 91 patients assessed the impact of postresuscitation goal directed/bundles of care (including blood pressure targets) on survival: One before
and after study of EGDT of 36 patients including a mean arterial pressure (MAP) target >80 mm Hg
showed no difference in mortality at hospital discharge (Gaieski 2009, 418). One before and after
observational study of a care bundle including 55 patients aiming for a MAP > 65 mmHg within 6 hours,
resulted in an in-hospital mortality of 55.2% (bundle) vs. 69.2% (prebundle) (P = 0.29). (Walters 2011,
360).
We suggest hemodynamic goals (e.g. MAP, SBP) are considered during post resuscitation care and as
part of any bundle of post-resuscitation interventions. (weak recommendation, low quality evidence).
There is insufficient evidence to recommend specific hemodynamic goals, such goals should be
considered on an individual patient basis and are likely to be influenced by post resuscitation status and
pre-existing morbidities that are considered during post resuscitation care. (weak recommendation, low
quality evidence).
CoSTR Attachments:
should-a-bundle-of-goal-directed-therapies-including-achieving-bp-goal-vs-no-bundlenot-achievingb2.doc
should-a-blood-pressure-target-achieved-vs-blood-pressure-target-not-achieved-be-used-for-adultswi.doc
ALS570_HaemodynamicsupportafterROSC_MP_15Jan2015corrected3.2.15.ppt
Impedance threshold device

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does use of an inspiratory impedance
threshold device (ITD) during CPR (I), compared with no ITD (C), change Survival with Favorable
at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?
Impedance Threshold Device + Standard CPR (I) vs Standard CPR (C): For the critical outcome of
neurologically intact survival at hospital discharge (assessed with Modified Rankin 3), there was one
RCT (Aufderheide 2011, 798) of high quality in 8718 out-of-hospital cardiac arrests that was unable to
demonstrate a clinically significant benefit from the addition of the ITD to standard CPR: RR 0.97 (95%
CI 0.82 to 1.15). For the critical outcome of survival to hospital discharge, there was one RCT
(Aufderheide 2011, 798) of high quality in 8718 out-of-hospital cardiac arrests that was unable to
demonstrate a clinically significant benefit from the addition of the ITD to standard CPR: RR 1 (95% CI
0.87 to 1.15). Impedance Threshold Device + Active Compression Decompression CPR (I) vs Active
Compression Decompression CPR (C): For the critical outcome of neurologically intact survival there
were no studies identified that compared the use of Impedance Threshold Device with Active
Compression Decompression CPR with Active Compression Decompression CPR in cardiac arrests. For the
critical outcome of survival to hospital discharge there were two RCTs (Plaisance 2000, 989, Plaisance
2004, 265) of very low quality (downgraded for imprecision and indirectness) that that were unable to
demonstrate a clinically significant benefit from the addition of the Impedance Threshold Device to Active
Compression Decompression CPR in a total of 421 out-of-hospital cardiac arrests: RR 0.91 (95% CI 0.07
to 12.7) (Plaisance 2000, 989) and RR 1.25 (0.5 to 3.1) (Plaisance 2004, 265). Impedance Threshold
Device + Active Compression Decompression CPR (I) vs Standard CPR (C): For the critical outcome of
neurologically intact survival at 12 months (assessed with CPC 2), there was one RCT (Frascone 2013,
1214) of very low quality (downgraded for risk of bias and suspected publication bias) in 2738 out-of-
hospital cardiac arrests that was unable to demonstrate a clinically significant benefit from the addition
of the ITD to ACD CPR (when compared with standard CPR): RR 1.34 (95% CI 0.97 to 1.85). For the
critical outcome of neurologically intact survival at hospital discharge (assessed with CPC 2), there was
one RCT (Frascone 2013, 1214, which incorporated data published in Aufderheide 2011, 301) of very low
quality (downgraded for risk of bias, inconsistency, and suspected publication bias) in 2738 out-ofhospital cardiac arrests that was unable to demonstrate a clinically significant benefit from the addition
of the ITD to ACD CPR (when compared with standard CPR): RR 1.28 (95% CI 0.98 to 1.69). For the
critical outcome of survival to 12 months, there was one RCT (Frascone 2013, 1214) of very low quality
(downgraded for risk of bias, and suspected publication bias) in 2738 out-of-hospital cardiac arrests that
was unable to demonstrate a clinically significant benefit from the addition of the ITD to ACD CPR (when
compared with standard CPR): RR 1.39 (95% CI 1.04 to 1.85, or from 2 more to 47 more per 1000). For
the critical outcome of survival to hospital discharge, there were two RCTs (Wolcke 2003, 2201 and
Frascone 2013, 1214 (which incorporated data published in Aufderheide 2011, 301)) of very low quality
(downgraded for risk of bias, indirectness and suspected publication bias) in a total of 2948 out-ofhospital cardiac arrests that were unable to demonstrate a clinically significant benefit from the addition
of the ITD to ACD CPR (when compared with standard CPR): RR 1.17 (95% CI 0.94 to 1.45)(Frascone
2013) and RR 1.41 (95% CI 0.75 to 2.66)(Wolcke 2003, 2201).
Impedance Threshold Device + Standard CPR (I) vs Standard CPR (C): We recommned against routine
use of ITD in addition to standard CPR (strong recommendation, high quality of evidence). Values and
preferences statement: In making this recommendation we place a higher value on not allocating
resources to an ineffective intervention over any yet to be proven benefit for critical or important
outcomes. Impedance Threshold Device + Active Compression Decompression CPR (I) vs Active
Compression Decompression CPR (C): We suggest against the routine use of ITD in addition to Active
Compression-Decompression CPR (weak recommendation, very low quality of evidence). Values and
resources to an ineffective intervention over any yet to be proven benefit for critical or important
outcomes. Impedance Threshold Device + Active Compression Decompression CPR (I) vs Standard CPR
(C): We suggest against the routine use of ITD with Active Compression-Decompression CPR as an
alternative to standard CPR (weak recommendation, very low quality of evidence). Values and
resources to an intervention with equivocal benefit for critical or important outcomes.
CoSTR Attachments:
ITDACDvsStandard2May2014.pdf
ITDACDvsACDEP1May2014.pdf
ITDnoITD2May2014.pdf
Induced Hypothermia
Question Type:
Intervention
Full Question:
Among patients with ROSC after cardiac arrest in any setting (P), does inducing mild hypothermia (target
temperature 32-34C) (I), compared with normothermia (36-37C) (C), change Survival with Favorable
Targeted temperature management (I) vs no targeted temperature management (C): Out-of-hospital
cardiac arrest with shockable rhythm: For the critical outcome of survival with good neurological
outcome, we have identified low quality evidence from one randomized control trial (RCT) [The
Hypothermia After Cardiac Arrest Study Group,2002;549] and one pseudorandomized trial
[Bernard;2002; 557] enrolling 275 and 77 patients, demonstrating a benefit in patients with out of
hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT)
as an initial rhythm. In these studies, cooling to 32-34 degrees Celsius compared to no temperature
management was associated with a risk ratio (RR) and odds ratio (OR) for good neurologic outcome at 6
months and hospital discharge of 1.4 (95% CI 1.08-1.81) and 2.65 (95% CI 1.02-6.88), respectively.
For the critical outcome of survival, low quality evidence in the larger study demonstrates benefit in
patients treated with induced hypothermia (RR for 180-day mortality 0.74, 95% CI 0.58-0.95) [The
Hypothermia After Cardiac Arrest Study Group,2002;549] while the other study found no significant
difference (51% vs 68% hospital mortality, p=0.145).[Bernard;2002; 557] Out-of-hospital cardiac arrest
with nonshockable rhythm: We found no randomized controlled trials comparing mild induced
hypothermia (32-34 degrees Celsius) to no temperature management in patients with OHCA with
pulseless electrical activity or asystole (i.e. nonshockable) as the initial rhythm.For the critical outcome
of survival with good neurologic outcome, we found three cohort studies including a total of 1,034
patients, providing overall very low-quality evidence for no difference in poor neurologic outcome in
patients with nonshockable OHCA (adjusted pooled OR, 0.90 [95% CI, 0.45 1.82].[Dumas; 2011; 877,
Testori;2011;1162, Vaahersalo;826; 2013] One additional retrospective study utilizing a large registry,
including 1830 patients, provided very low quality evidence for an increase in poor neurologic outcome in
patients with nonshockable OHCA.[Mader;2014;21] This data was not pooled with the above studies and
an adjusted OR was not included in the CoSTR due to the lack of temperature data, limited patient
information, and inconsistent results within the study. For the critical outcome of survival, we found
very low quality evidence of a benefit in mortality at 6 months (OR 0.56, 95% CI 0.34-0.93) from one of
these studes.[Testori;2011;1162] In-hospital cardiac arrest: We found no RCTs comparing mild induced
hypothermia (32-34 degrees Celsius) to no temperature management in patients with in-hospital cardiac
arrest (IHCA). For the critical outcome of survival to hospital discharge, we found very low quality
evidence in one retrospective cohort study including 8316 patients that showed no benefit in patients
with IHCA of any initial rhythm who were treated with targeted temperature management vs. no active
temperature management (OR 0.9, 95% CI 0.65-1.23).[Nichol;2013;620] For the critical outcome of
neurologically favorable survival, we found very low quality evidence from the same observational
study showing no benefit (OR 0.93, 95% CI 0.65-1.32). This evidence was downgraded for high
probability of selection bias, residual confounding, and a low prevalence of patients (2.6%) receiving the
intervention. Note: Although we found numerous observational studies on the implementation of
temperature management, these data are extremely difficult to interpret in light of other changes in
post-cardiac arrest care that accompanied implementation, making it impossible to isolate the effect of
temperature on outcomes after cardiac arrest. For this reason, we excluded all before and after studies.
Other observational studies with concurrent controls also represent low quality evidence due to residual
confounding and other factors. We therefore did not include these in the consensus on science, except
for specific patient populations lacking higher quality (i.e. RCT) evidence. Is there evidence for an ideal
temperature (I) when using targeted temperature management? For the critical outcomes of survival
and survival with good neurologic outcome, we found moderate quality evidence from one RCT
including 939 patients. This study compared cooling to 33 degrees Celsius compared to tight
temperature control at 36 degrees Celsius in adult patients with OHCA of any initial rhythm except
unwitnessed asystole, and found no benefit (HR for mortality at end of trial 1.06, 95% CI 0.89-1.28; RR
for death or poor neurologic outcome at 6 months 1.02, 95% CI 0.88-1.16).[Nielsen;2013;2197] For the
critical outcome of survival with good neurologic outcome we found low quality evidence in one
additional small pilot RCT enrolling 36 patients comparing 32 vs 34 degrees Celsius in patients with
OHCA VT/VF or asystole.[Lopez-de-sa;2012;2826] This study found no benefit (neurologically intact
survival 44.4% vs 11.1%, p=0.12), although with only 36 patients it was underpowered.
We recommend targeted temperature management as opposed to no targeted temperature management
for adults with OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong
recommendation, low-quality evidence). We suggest targeted temperature management as opposed to
no targeted temperature management for adults with OHCA with an initial nonshockable rhythm (weak
recommendation, very low-quality evidence) who remain unresponsive after ROSC. We suggest targeted
temperature management as opposed to no targeted temperature management for adults with IHCA
(weak recommendation, very low-quality evidence) with any initial rhythm who remain unresponsive
after ROSC. We recommend selecting and maintaining a constant, target temperature between 32C and
36C for those patients in whom temperature control is used (strong recommendation, moderate-quality
evidence). Whether certain subpopulations of cardiac arrest patients may benefit from lower (32-34oC)
or higher (36oC) temperatures remains unknown, and further research may help elucidate this.
CoSTR Attachments:
ALS 790. TTM Main. Full presentation. Dallas 2015.pptx
ALS 790. GRADE Tables - TTM main question.pdf
Induced Hypothermia (duration)
Question Type:
Intervention
Full Question:
In patients with ROSC after cardiac arrest in any setting (P), does induction and maintenance of
hypothermia for any duration other than 24 hours (I), compared with induction and maintenance of
hypothermia for a duration of 24 hours (C), change Survival with Favorable neurological/functional
60 days, 180 days AND/OR 1 year (O)?
We found no human interventional studies comparing different durations of targeted temperature
management after cardiac arrest with ROSC. One observational trial provided overall very low-quality
evidence for no difference in duration of hypothermia in those with a good versus a poor neurologic
outcome [Yokoyama 2011 1063]. One observation trial provided overall very low-quality evidence for no
difference in mortality or poor neurological outcome with 24 hours compared to 72 hours of hypothermia
[Lee 2014 297]. Previous trials for targeted temperature management ranged from 12 to 28 hours
depending on the trial [Bernard 2002 557, HACA 2002 549, Nielsen 2013 2197]. One trial provided strict
normothermia (< 37.5 oC) after rewarming until 72 hours after ROSC [Nielsen 2013 2197]. However this
intervention was applied to both groups and therefore treatment effect cannot be assessed.
We suggest that if targeted temperature management is used, duration should be at least 24 hours as
done in the two largest previous RCTs [HACA 2002 549, Nielsen 2013 2197] (weak recommendation,
very low-quality evidence).
CoSTR Attachments:
ALS 791. TTM Duration. Rapid fire presentation. Dallas 2015.pptx
ALS 791. TTM Duration. Full presentation. Dallas 2015.pptx
Induced Hypothermia (timing)

Question Type:
Intervention
Full Question:
Among patients with return of pulses after cardiac arrest in any setting (P), does induction of
hypothermia before some time point (e.g. 1 hour after ROSC or prior to hospital arrival) (I), compared
with induction of hypothermia after that time point (C), change Survival with Favorable
Seven RCTs were identified for inclusion from 2286 studies generated from the search. Five [Kim 2007
3064, Kamarainen 2009 900, Bernard 2010 737, Bernard 2012 747, Kim 2014 45] of the 7 studies used
cold intravenous fluids after ROSC to induce hypothermia, one study used cold intravenous fluid during
resuscitation [Debaty 2014 1832] and one study used intra-arrest intranasal cooling [Castren 2012
729].The volume of cold fluid ranged from 20 30 ml/kg and up to 2 liters though some patients did not
receive the full amount prior to hospital arrival. One small feasibility trial was not included [Callaway
2002 159]. All 7 included studies suffered from the unavoidable lack of blinding of the clinical team, and
3 also failed to blind the outcomes assessors. Five of the studies, enrolling a total of 1,867 patients with
OHCA, evaluated the outcome of poor neurologic outcome [Kamarainen 2009 900, Castren 2012 729,
Bernard 2010 737, Bernard 2012 747, Kim 2014 45]. Meta-analysis of these studies showed that
initiation of induced hypothermia in the prehospital environment did not differ from no initiation of
prehospital induced hypothermia for poor neurologic outcome (RR, 1.00; 95% CI, 0.951.06). All 7 trials
examined the outcome of mortality, and meta-analysis of the total of 2,237 patients provided moderatequality evidence demonstrating no overall difference in mortality for patients treated with prehospital
cooling (RR, 0.98; 95% CI, 0.921.04) compared to those who did not receive prehospital cooling. When
reviewed individually, none of the trials found an effect on either poor neurologic outcome or mortality.
Meta-analysis of 4 RCTs that examined the outcome of re-arrest demonstrated an increased risk for rearrest among patients who received prehospital induced hypothermia (RR, 1.22; 95% CI, 1.011.46)
[Kim 2007 3064, Kamarainen 2009 900, Bernard 2012 747, Kim 2014 45]. This result was driven by
data from the largest trial [Kim 2014 45]. Six trials included pulmonary edema as an outcome. Three of
these recorded no pulmonary edema in either group. The remaining three did record patients who had
pulmonary edema. Two small pilot trials [Kim 2007 3064, Depaty 2014 1832] found no statistically
significant difference between the groups whereas the larger trial by Kim et al. found an increase in
pulmonary edema in patients who received prehospital cooling (RR, 1.34; 95% CI, 1.15-1.57) [ Kim
2014 45].
We recommend against routine use of prehospital cooling with rapid infusion of large volumes of cold
intravenous fluid immediately after ROSC (strong recommendation, moderate-quality evidence).
CoSTR Attachments:
ALS 802. GRADE Tables - TTM timing question.pdf
ALS 802. TTM Timing. Full presentation. Dallas 2015.pptx
Lipid Therapy for Cardiac Arrest

Question Type:
Intervention
Full Question:
In adult patients with cardiac arrest due to suspected drug toxicity (e.g. local anesthetics, tricyclic
antidepressants, or others) (P), does administration of intravenous lipid (I), compared with no
intravenous lipid (C), change Survival with Favorable neurological/functional outcome at discharge, 30
1 year, ROSC (O)?
For the critical outcomes of neurologically intact survival and survival and for the important outcome of
ROSC, we have not identified any studies of sufficient quality or relevance to the PICO question to
include in this review.
Due to a lack of human comparative studies in cardiac arrest and peri-arrest states, we are unable to
make any evidence-based treatment recommendation about the use of intravenous lipid emulsion to
treat toxin-induced cardiac arrest.
CoSTR Attachments:
ALS-834 Lipid Therapy for Cardiac Arrest 2015-02-03 posted for public comment.pdf
Mechanical CPR Devices

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does Automated mechanical CPR devices (I),
compared with Standard Manual CPR (C), change Survival with Favorable neurological/functional
For the critical outcome of survival to hospital discharge with good neurologic outcome (defined as CPC
1-2 or mRS 0-3), we have identified moderate quality evidence from 3 RCTs enrolling 7582 OHCA
patients showing variable results (Hallstrom 2006 2620, Wik 2014 741, Rubertsson 2013 53). One study
(Hallstrom 2006 2620) (n=767) demonstrated harm with the use of a load-distributing band mechanical
chest compression device compared to manual chest compressions (7.5% of patients in the control
group versus 3.1% in the intervention group, p=0.006). Two other RCTs (Wik 2014 741, Rubertsson
2013 53) (n=6820), one using a load-distributing band and the other a LUCAS (Lund University Cardiac
Arrest System), did not demonstrate benefit or harm when compared with manual chest compressions.
For the critical outcomes of survival at 30 days with good neurologic outcome and survival at 180 days
with good neurologic outcome, we identified moderate quality evidence from 1 RCT (Rubertsson 2013
53) using a LUCAS device and enrolling 2589 OHCA patients that did not demonstrate benefit or harm
when compared with manual chest compressions. For the critical outcome of survival to hospital
discharge, we identified moderate quality evidence from 5 RCTs (Hallstrom 2006 2620, Lu 2010 496,
Rubertsson 2013 53, Smekal 2011 702, Wik 2014 741) enrolling 7734 OHCA patients and 150 inhospital cardiac arrest patients showing heterogeneous results. One study of patients with in-hospital
cardiac arrests (Lu 2010 496) (n=150) demonstrated benefit with use of a piston device compared with
manual chest compressions (32.9% versus 14.7%, p=0.02). Two other RCTs (Rubertsson 2013 53,
Smekal 2011 702) did not demonstrate benefit or harm. One large RCT (Wik 2014 741) (n=4231) using
a load-distributing band device demonstrated equivalence when compared with high-quality manual
chest compressions. For the critical outcome of survival to 30 days we identified moderate quality
evidence from two RCTs (Rubertsson 2013 53, Perkins 2014 1, n=7060) using the LUCAS device
showing no benefit or harm when compared with manual chest compressions where quality of
compressions in the manual arm was not measured. For the critical outcome of survival to 180 days, we
identified moderate quality evidence from one RCT (Rubertsson 2013 53) using a LUCAS device enrolling
2589 OHCA patients showing no benefit or harm when compared with manual chest compressions where
quality of chest compressions in the manual arm was not measured. For the critical outcome of survival
to 1 year, we identified moderate quality evidence from one cluster RCT (Perkins 2014 1) using the
LUCAS device showing no benefit or harm when compared with manual chest compressions. For the
important outcome of return of spontaneous circulation, we identified low quality evidence from 7 RCTs
enrolling 11,638 cardiac arrest patients (in-hospital and OHCA) (Dickinson 1998 289, Halperin 1993 762,
Lu 2010 496, Perkins 2014 1, Rubertsson 2013 53, Smekal 2011 702, Wik 2014 741) . Three studies
(Dickinson 1998 289, Halperin 1993 762, Lu 2010 496) (n=201) demonstrated benefit with mechanical
chest compression devices. One study (Wik 2014 741)(n=4231) demonstrated harm with mechanical
devices however there was no adjustment for interim analyses. Three studies (Perkins 2014 1,
Rubertsson 2013 53, Smekal 2011 702)(n=7206) did not demonstrate benefit or harm when compared
to manual chest compressions.
We suggest mechanical chest compression devices should not be considered the standard of care for
cardiac arrest patients, but can be considered a reasonable alternative to high quality manual chest
compressions in some settings (weak recommendation, moderate quality of evidence). Values and
Preferences Statement: In making this recommendation we place value on data from a large, highquality RCT demonstrating equivalence between high quality manual chest compressions and mechanical
chest compressions. Local considerations such as relative costs and resource availability for maintenance
of high quality manual chest compressions and mechanical chest compression device implementation
should guide decisions around which mode of chest compression delivery is most appropriate. Also, there
may be scenarios not directly addressed in the literature reviewed to support this treatment
recommendation such as CPR in a moving ambulance, in the angiography suite or during preparation for
ECLS, where mechanical chest compressions are more practical.
CoSTR Attachments:
MEch CPR ev profile table Jan 22 2015.docx
Opioid toxicity
Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest or respiratory arrest due to opioid toxicity in any setting (P),
does any adjunct therapy (e.g. naloxone, bicarbonate, or other drugs) (I), compared with usual ALS with
no adjunct therapy (C), change Survival with Favorable neurological/functional outcome at discharge, 30
1 year, ROSC (O)?
For the important outcome of Survival with Favorable neurological/functional outcome at discharge, 30
days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days
AND/OR 1 year, ROSC, following opioid induced cardiac arrest, we found 0 publications providing no data
upon which to make a recommendation beyond standard ALS care For the important outcome of
AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC, following
opioid induced respiratory arrest, 12 publications were included 5 assessed the route of naloxone
administration, 7 assessed the safety of naloxone use or were observational studies of naloxone use.
We recommend the use of naloxone by intravenous, intramuscular, subcutaneous, intraosseous, or
intranasal routes in respiratory arrest presumed due to opioid toxicity. (strong recommendation, very
low quality of evidence). Dosage of naloxone varies by route. We can make no recommendation
regarding the modification of standard ALS in opioid induced cardiac arrest.
CoSTR Attachments:
C2015 Rapid Fire ILCOR OPIATE ALS Slide Template.1.7.15.potx
Organ donation
Question Type:
Intervention
Full Question:
Among adults and children who are receiving an organ transplantation in any setting (P), does an organ
retrieved from a donor who has had CPR (e.g. donor dies on ICU after intial successful CPR , or donation
after unsuccessful CPR) (I), compared with an organ retrieved from a donor who did not have CPR (C),
change increase survival rates, Complication Rate (O)?
Consensus on Science Donors with Prior CPR Two papers reported the mean yield of organs procured
from donors who had been resuscitated by CPR prior to donation was 3.9 (Faucher 2014) or 2.9 (Orioles
2013). For the critical outcome of immediate graft survival, low quality evidence from non-randomized
studies did not detect any worse outcome when donors have had CPR and resuscitation for adult hearts
(3239 organs, 7 studies), pediatric hearts (557 organs, 4 studies), adult lungs (1031 organs, 4 studies),
pediatric lungs (105 organs, 1 study), adult kidneys (5,000 organs, 2 studies), pediatric kidneys (1122
organs, 2 studies), adult livers (2,911 organs, 3 studies), pediatric livers (689 organs, 2 studies), adult
intestines (25 organs, 2 studies), and pediatric intestines (79 organs, 1 study) For the important
outcome of graft survival for 1 year, low quality evidence from non-randomized studies did not detect
any worse outcome when donors have had CPR and resuscitation for adult hearts (3230 organs, 8
studies), pediatric hearts (1605 organs, 8 studies), adult lungs (1031 organs, 4 studies), pediatric lungs
(105 organs, 1 study), adult kidneys (5,000 organs, 2 studies), pediatric kidneys (1122 organs, 2
studies), adult livers (2,911 organs, 3 studies), pediatric livers (689 organs, 2 studies), adult intestines
(25 organs, 2 studies), and pediatric intestines (79 organs, 1 study) For the important outcome of graft
survival for 5 years, low quality evidence from non-randomized studies did not detect any worse
outcome when donors have had CPR and resuscitation for adult hearts (3230 organs, 8 studies),
pediatric hearts (1537 organs, 8 studies), adult lungs (1031 organs, 4 studies), pediatric lungs (105
organs, 1 study), adult kidneys (5,000 organs, 2 studies), pediatric kidneys (1122 organs, 2 studies),
adult livers (2,911 organs, 3 studies), pediatric livers (689 organs, 2 studies), adult intestines (25
organs, 2 studies), and pediatric intestines (79 organs, 1 study) Donors with ongoing CPR (uncontrolled
on-heart beating donors or uncontrolled donation after circulatory death) Two papers reported the mean
number of organs procured from donors with ongoing CPR was 1.5 (Fondevilla 2012) and 3.2 (MateosRodriguez 2012) For the critical outcome of immediate graft survival, low quality evidence from nonrandomized studies did not detect any worse outcome when organs were recovered from non-heart
beating donors with ongoing CPR compared to other types of donors for adult kidneys (203 organs, 4
studies) or adult livers (64 organs, 4 studies). For the important outcome of graft survival for 1 year, low
quality evidence from non-randomized studies did not detect any worse outcome when organs were
recovered from non-heart beating donors with ongoing CPR compared to other types of donors for adult
kidneys (199 organs, 3 studies) or adult livers (60 organs, 3 studies). For the important outcome of graft
survival for 5 years, low quality evidence from non-randomized studies did not detect any worse
outcome when organs were recovered from non-heart beating donors with ongoing CPR compared to
other types of donors for adult kidneys (177 organs, 2 studies) or adult livers (34 organs, 1 study).
Treatment Recommendation: 1. We recommend that all patients who have restoration of circulation after
CPR and who subsequently progress to death be evaluated for organ donation (strong recommendation,
low quality of evidence). In making this recommendation, we consider the absence of any evidence of
worse graft function from donors with antecedent CPR, the desirability of providing more organs to
waiting recipients, and the absence of any risk to the donor. As in all organ donation, the function of the
donated organ determines whether procurement and transplantation proceed. Therefore, there is also
precaution to ensure the safety of the recipient. 2. We suggest that patients who fail to have restoration
of circulation after CPR and who would otherwise have termination of efforts be considered candidates
for kidney or liver donation in settings where programs exist (weak recommendation, low quality of
evidence). In making this recommendation, we consider the evidence that kidney grafts obtained from
donors with ongoing CPR can function at rates comparable to kidneys obtained from other donors, and
that recipients can safely tolerate delayed graft function that is common with kidneys obtained in this
manner. We also consider the immediate life-saving potential of liver grafts, which offsets the potentially
greater rate of long-term graft failure in livers obtained from donors with ongoing CPR.
CoSTR Attachments:
SummarofBiasAssessmentsOrganDonationFinal.xlsx
AgreementDisagreement_Updated_Reasons_final.xlsx
TableResultsFinal.docx
ILCORDataCollectionFormOrganDonationFinal.xls
Oxygen dose after ROSC in adults

Question Type:
Intervention
Full Question:
Among adults who have ROSC after cardiac arrest in any setting (P), does an inspired oxygen
concentration titrated to oxygenation (normal oxygen saturation or partial pressure of oxygen) (I),
compared with the use of 100% inspired oxygen concentration (C), change survival to 30 days with
good neurological outcome, survival to hospital discharge with good neurological outcome, improve
survival, survival to 30 days, survival to hospital discharge (O)?
1. 30% inspired oxygen for 60 minutes after ROSC vs. 100% inspired oxygen for 60 minutes after ROSC
Survival to discharge with favourable neurological outcome (CPC 1 or 2): [1 study, observational,
Kuisma 2006 199]. For the critical outcome of survival to hospital discharge with favourable neurological
outcome (CPC 1 or 2) we have identified very low quality evidence (downgraded for risk of bias,
imprecision, lack of blinding, indirectness) from one RCT [Kuisma 2006 199] enrolling 32 OHCA (of which
4 excluded) patients that showed no difference between 30% inspired oxygen for 60 minutes after ROSC
vs.100% inspired oxygen for 60 minutes after ROSC (8/14 vs. 6/14, unadjusted RR for survival1.33
[95% CI 0.63 to 2.84] p=0.46) . Survival to hospital discharge: [1 study, observational, Kuisma 2006
199]. For the critical outcome of survival to hospital discharge we have identified very low quality
evidence (downgraded for small numbers, lack of blinding, indirectness, misallocation of patients) from
one RCT [Kuisma 2006 199] enrolling 32 OHCA (of which 4 excluded) patients that showed no difference
between 30% inspired oxygen for 60 minutes after ROSC and 100% inspired oxygen for 60 minutes of
after ROSC (10/14 vs. 10/14, unadjusted RR for survival 1.0 [95% CI 0.63 to 1.60] p=1.00). 2.
Hyperoxia vs. Normoxia Survival with favourable neurological outcome (CPC 1 or 2) at 12 months: [1
study , observational, Vaahersalo 2014 1463] For the critical outcome of survival with favourable
neurological outcome (CPC 1 or 2) at 12 months we have identified very low quality evidence from 1
study [Vaahersalo 2014 1463] (downgraded for very serious risk of bias, and indirectness) that showed
no harmful effect from hyperoxia during the first 24 hours of ICU care. Survival to discharge with
favourable neurological outcome (CPC 1 or 2): [5 studies, observational, Kilgannon 2010 2165, Bellomo
2011 R90, Janz 2012 3135, Roberts 2013 2107, Elmer 2014] For the critical outcome of survival to
hospital discharge with favourable neurological outcome (CPC 1 or 2) we have identified very low quality
evidence (downgraded as very serious bias and serious inconsistency, indirectness, confounding)) from 5
observational studies with conflicting results [2 showed hyperoxia worse than normoxia]. Studies
reported CPC 1 or 2 outcomes at discharge: Janz [2012 3135] showed in a single centre study of 170
ICU patients treated with therapeutic hypothermia that the maximum PaO2 in the first 24 h after arrest
was associated with a worse outcome (CPC 1 or 2) (poor neurological status at hospital discharge,
adjusted OR 1.485 [95% CI1.032 2.136] P = .033). Roberts [2013 2107] showed in a single centre
study of 193 ICU patients that the first PaO2 after ROSC was not associated with outcome (hyperoxia
adjusted OR for poor neurological outcome 1.05 [95% CI 0.45-2.42] P=0.911). Elmer [2014] showed
in a single centre study of 184 ICU patients that oxygen exposure over first 24 h of ventilation was not
associated with outcome with unadjusted and adjusted outcomes [effect size cannot be estimated from
data]. Two studies did not report CPC outcomes, and used other measures as a surrogate marker:
Kilgannon [2010 2165] reported worse independent functional survival at hospital discharge (hyperoxia
vs. normoxia 124/1156 vs. 245/1171 [29 vs. 38%], unadjusted OR 0.45 [95%CI 0.36 -0.58] P
300mmHg in 1st 24 h after arrest) and normoxia (22/49 vs. 25/70, unadjusted OR 0.68 [95% CI 0.32 to
1.44] P=0.31) for 30 day survival or survival to discharge (20/49 vs. 24/70, unadjusted OR 0.76 [95%
CI 0.36 to 1.61] P=0.47). Elmer [2014] reported that of 184 ICU patients, 36 % were exposed to
severe hyperoxia, there overall mortality was 54 %, and severe hyperoxia, was associated with
decreased survival in both unadjusted and adjusted analysis [adjusted odds ratio (OR) for survival 0.83
per hour exposure (95% CI 0.69-0.990, P = 0.04]. Survival to ICU discharge: [2 observational studies,
Ihle 2013 186, Nelskyla 2013] For the important outcome of survival to ICU discharge we have identified
very low quality evidence (downgraded as very serious bias, serious indirectness, confounding) from 2
observational studies that showed no harm from hyperoxia: Ihle [2013 186] showed in a data linkage
study of worse PaO2 (highest/lowest) in first 24 on ICU hyperoxia was not associated with outcome (ICU
mortality 35% vs. 32% for hyperoxia vs. normoxia, unadjusted OR 1.16 [95%CI 0.56 2.40] P=0.68).
One observational study [Nelskyla 2013, survival to 30 days] enrolling 122 ICU admissions patients that
showed no difference between patients with hyperoxia (PaO2 > 300mmHg in 1st 24 h after arrest) and
normoxia (ICU discharge 53% vs. 46%, adjusted OR 0.75 [95%CI 0.36-1.55] P=0.43). 3. Hypoxia vs.
normoxia Survival to hospital discharge (or survival to 30 days): [3 observational studies, Kilgannon
2010 2165, Bellomo 2011 R90, Ihle 2013 186] For the critical outcome of survival to discharge (or
survival to 30 days) we have identified very low quality evidence (downgraded as very serious bias and
serious indirectness, confounding) from 3 observational studies that showed : Kilgannon [2010 2165]
showed a worse outcome with hypoxia vs. normoxia based on the first ICU PaO2 (57 vs. 45%, adjusted
OR hypoxia exposure 1.3 [95%CI 1.1-1.5] P = 0.009). Bellomo [2011 R90] showed a hypoxia vs.
normoxia (based on the worse PaO2 in first 24 h on ICU) hospital mortality of 60 vs. 47% (hypoxia/poor
O2 exchange vs. normoxia, OR hospital mortality 1.2 (1.1 to 1.4) P= 0.002). This paper also reported
discharge to home outcomes (hypoxia/poor O2 exchange vs. normoxia 26 vs. 24%). Ihle [2013 186]
showed in a data linkage study of worse PaO2 (highest/lowest) in first 24 on ICU no difference in
outcome between hypoxia and normoxia (for in hospital mortality, 51 vs. 41%, adjusted OR hypoxia vs.
normoxia 0.93 [95%CI 0.47-1.87]. Survival to ICU discharge: [1 observational study, Ihle 2013 186] For
the important outcome of survival to ICU discharge we have identified very low quality evidence
(downgraded as very serious bias and serious indirectness, confounding) from 1 observational study:
Ihle [2013 186] showed in a data linkage study of worse PaO2 (highest/lowest) in first 24 on ICU
hypoxia was associated with a worse unadjusted outcome (ICU mortality 49% vs. 32% for hypoxia vs.
normoxia, unadjusted OR 2.15 [95% CI 1.23 3.77] P=0.008). RR 0.74 (95% CI 0.56 -0.96) worse
with hypoxia.
We recommend the avoidance of hypoxia in adults with ROSC after cardiac arrest in any setting (strong
recommendation, very low quality evidence). We suggest the avoidance of hyperoxia in adults with
ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence). We
suggest the use of 100% inspired oxygen until the arterial oxygen saturation or the partial pressure of
arterial oxygen can be measured reliably in adults with ROSC after cardiac arrest in any setting (weak
recommendation, very low quality evidence).
CoSTR Attachments:
CoS and TR for O2 after ROC_JS3Jan2015.docx
ALS448_OxygendoseafterROSC_JS_3Jan2015.ppt
Oxygen dose during CPR

Question Type:
Intervention
Full Question:
In adults with cardiac arrest in any setting (P), does administering a maximal oxygen
concentration (e.g. 100% by face mask or closed circuit) (I), compared with no supplemental oxygen
(e.g. 21%) or a reduced oxygen concentration (e.g. 40-50%) (C), change Survival with Favorable
There are no adult human studies that directly compare maximal inspired oxygen with any other inspired
oxygen concentration. For the critical outcome of survival to hospital discharge with favourable
neurological outcome (CPC 1 or 2) we identified very low quality evidence (downgraded for very serious
risk of bias and very serious indirectness, and serious imprecision) from 1 observational study
[Spindelboeck 2013 770] enrolling 145 OHCA patients who had a PaO2 measured during CPR that
showed no difference between an intermediate PaO2 and low PaO2 [11/83 vs. 1/32, RR 4.2 (95 CI 0.57
31.52) P = 0.16], or between a high PaO2 and low PaO2 [7/30 vs. 1/32 RR 7.45 (95 CI 0.98 57.15)
P = 0.053]. For the important outcome of ROSC we identified very low quality evidence (downgraded for
very serious risk of bias and very serious indirectness, and serious imprecision) from 1 observational
study [Spindelboeck 2013 770] enrolling 145 OHCA patients who had a PaO2 measured during CPR that
showed improved ROSC in those with a higher PaO2; [Intermediate PaO2 vs. Low PaO2 47/83 vs. 7/32
RR 2.59 (95% CI 1.31 5.12) P = 0.006], [High PaO2 vs. Low PaO2 25/30 vs. 7/32 RR 3.81 (95% CI
1.94 7.48) P = 0.0001], [High PaO2 vs. Intermediate PaO2 25/30 vs. 47/83, RR 1.47 (95% CI 1.15
1.88) P=0.002]. In the single identified study [Spindelboeck 2013 770] all patients had tracheal
intubation and received 100% inspired oxygen during CPR. The worse outcomes associated with a low
PaO2 during CPR could be an indication of illness severity.
We suggest the use of the maximal feasible inspired oxygen concentration during CPR (weak
recommendation, very low quality evidence). In making this recommendation we have considered the
limited available evidence, the need to correct tissue hypoxia during CPR, and see no reason to change
the current treatment recommendation, which includes use of 100% inspired oxygen during adult cardiac
arrest.
CoSTR Attachments:
ALS 889 OxygenduringCPR_JS3Jan2014.docx
O2duringCPR_Soar_TF_30jan2015.ppt
Pregnancy and cardiac arrest

Question Type:
Intervention
Full Question:
Among pregnant women who are in cardiac arrest in any setting (P), does any specific intervention(s)
(I), compared with standard care (usual resuscitation practice) (C), change Survival with Favorable
We found no comparative studies of doing or not doing uterine displacement for women in cardiac arrest
prior to delivery. We found no comparisons of different maneuvers (e.g., manual displacement vs. left
pelvic tilt) to achieve optimal uterine displacement for women in cardiac arrest prior to delivery.
Physiologic reviews and studies of uterine displacement maneuvers in non-arrest populations of pregnant
women support that uterine displacement might be physiologically beneficial for women in cardiac arrest
(Cyna AM, Cochrane 2006, CD002251). Any benefit would have to be weighed against the potential
interference with usual resuscitation care. For the critical outcomes of survival with favorable
neurological/functional outcome at discharge, 30 days, 60 days, 180 days, AND/OR 1 year, and survival
only at discharge, 30 days, 60 days, 180 days, AND/OR 1 year, and the important outcomes of ROSC,
we found three observational studies of 154 subjects collectively (Einav, 2012, 1191, Dijkman, 2010,
282, Baghirzada, 2013, 1077) that provided very low quality evidence comparing cardiac arrest
resuscitation with or without perimortem caesarian section. Procedures to ascertain cases and controls in
these studies were sufficiently different that the pooled comparison of any of the assigned outcomes
would be considered inappropriate.
We suggest delivery for women in cardiac arrest in the second half of pregnancy. (very weak
recommendation, very low quality) There is insufficient evidence to define a specific time interval by
which delivery should begin. High quality usual resuscitation care and therapeutic interventions that
target the most likely cause(s) of cardiac arrest remain important in this population. Value and
Preferences Statement: In making this statement, we place value on maternal and neonatal survival, on
the absence of data on uterine displacement in women with cardiac arrest, and on our uncertainty about
the absolute effect of either uterine displacement or perimortem delivery on any of the assigned
outcomes.
CoSTR Attachments:
Mhyre Zelop Pregnancy Excel Tables 2-9-14.xlsx
ALS 436 Pregnancy - Dallas 1-22-2015.pptx
ALS 436 Pregnancy text and endnote 1-15-15.docx
Prognostication in hypothermia
Question Type:
Prognostic
Full Question:
Among adults with ROSC who are treated with hypothermia, (P), does any clinical variable when
normal (e.g. 1. Clinical Exam, 2. EEG, 3. SSEP, 4. Imaging, 5. Other) when present (I), compared with
any clinical variable when abnormal (C), change Survival with Favorable neurological/functional outcome
at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days,
180 days AND/OR 1 year (O)?
Clinical Examination: In patients who are comatose after resuscitation from cardiac arrest and who are
treated with targeted temperature management, bilaterally absent pupillary reflexes to light at 72 or
later from ROSC predict a poor outcome (death, vegetative state or severe cerebral disability) with very
high precision (FPR 0[0-3]%). Bilaterally absent corneal reflexes at 72h or later from ROSC is also an
accurate predictor of poor outcome, but it is less specific (FPR 2[0-7]%). Both these predictors have a
low sensitivity (. 25%). Bilaterally absent or extensor motor response to pain at 36h or later from ROSC
has a relatively high sensitivity for prediction of poor outcome (70[65-74]%). However, its false positive
rate is also high (10[7-15]%). There are little data at present on combination of clinical signs. Presence
of myoclonus within 72h from cardiac arrest is inconsistently associated with poor outcome (FPR 6%;
95%CIs 3-9). A prolonged, continuous and generalised myoclonus (status myoclonus) within 72h from
cardiac arrest predicts poor outcome with high precision (FPR 0 [0-4[%) but low sensitivity (16%;
95%CIs 11-22). Rare cases of good outcome in patients with an early-onset status myoclonus have been
reported. Predictors based on clinical examination, especially corneal reflex and motor response to pain,
may be affected by sedation or paralysis. Blinding of the treating team is very difficult to achieve for
predictors based on clinical examination, which implies a risk of self-fulfilling prophecy.
Electrophysiology: In patients who are comatose after resuscitation from cardiac arrest and who are
treated with targeted temperature management a bilaterally absent N20 wave accurately predicts a poor
neurological outcome after rewarming (at 72h from ROSC) (FPR 1[0-3]%) while prediction during TTM is
less reliable (FPR 2[0-4]%). Absence of EEG background reactivity during TTM is inconsistently
associated with a poor neurological outcome (FPR 2 [1-7]%) while after rewarming at .72 h from ROSC it
predicts a poor outcome with 0[0-3]% FPR. Limitations of EEG reactivity include being operator
dependent and non-quantitative, and lacking standardization. Presence of epileptiform discharges on
EEG, both during TH or after rewarming is inconsistently associated with poor neurological outcome.
Presence of electrographic seizures or status epilepticus, either during TTM or after rewarming is almost
invariably associated with poor outcome. The definition of epileptiform activity and status epilepticus is
inconsistent among studies. Limited evidence shows that prognosis is worse when status epilepticus is
associated to a non-continuous background or absence of reactivity. A flat or low-voltage EEG was
inconsistently associated with poor outcome. Timing and definitions of low voltage was inconsistent
among studies. A lowest BIS value =0 during TTM, corresponding to a flat or very low voltage EEG
during TH is inconsistently associated with poor outcome (FPR from 0% to 10%). BIS is affected by
interference from muscular artefacts, which restricts its use in patients who are sedated and paralysed
during TTM treatment. The amplitude of the EEG signal may be affected on a variety of technical
conditions such as skin and scalp impedance, inter-electrode distances, size, type and placement of the
exploring electrodes, and type of filters adopted.49 Use of EEG grading, brainstem auditory evoked
potentials and pain-related somatosensory evoked potentials has been documented only in single studies
and their predictive value needs confirmation from other studies. Biomarkers: In patients who are
comatose after resuscitation from cardiac arrest and who are treated with targeted temperature
management, high and increasing concentrations of biomarkers are associated with poor outcome.
However, the biomarkers thresholds which predict a poor neurological outcome with 0% FPR vary
between studies. Advantages of biomarkers over other predictors such as EEG and clinical examination
include quantitative results and likely independence from the effects of sedatives. Moreover, in most
prognostication studies biomarkers were not used as a criterion for WLST (see Table 2). S-100B is less
well documented than NSE. Imaging: In patients who are comatose after resuscitation from cardiac
arrest and who are treated with targeted temperature management the presence of global cerebral
oedema or a reduction of the grey/white matter interface measured as the GWR within 2 hours from
ROSC predicted poor outcome with 0% FPR, but the GWR thresholds for 0% FPR varied among studies,
according to the area studied and the measurement technique. In patients who are comatose after
resuscitation from cardiac arrest and who are treated with targeted temperature management the
presence of diffuse hypoxic-ischemic injury detected by DWI changes and quantified by ADC from 2 to 6
days from ROSC predicted poor outcome with 0% FPR. The ADC thresholds for 0% FPR varied among
studies, according to the cerebral area studied and the measurement technique. All studies on
prognostication after cardiac arrest using imaging have a small sample size with a consequent low
precision, and are prone to selection bias, since the imaging studies were performed at discretion of
treating physician, which may have caused a selection bias and overestimated their performance.
Imaging studies depend partly on subjective human decision in identifying the region of interest to be
studied and in the interpretation of results.
Clinical examination:In patients who are comatose after resuscitation from cardiac arrest and who are
treated with targeted temperature management, we recommend using bilaterally absent pupillary light
reflexes or the combined absence of both pupillary and corneal reflexes at .72 h from ROSC to predict
poor outcome. We do not suggest using an absent or extensor motor response to pain (M.2) alone to
predict poor outcome, given its high false positive rate. However, due to its high sensitivity, this sign
may be used to identify the population with poor neurological status needing prognostication or to
predict poor outcome in combination with other more robust predictors. We suggest using the presence
of a status myoclonus within 72 h from ROSC in combination with other predictors for prognosticating a
poor neurological outcome. We suggest prolonging the observation of clinical signs when interference
from residual sedation or paralysis is suspected, so that the possibility of obtaining false positive results
is minimized. We recommend that the earliest time to prognosticate a poor neurological outcome is
72hrs after ROSC, and should be extended longer if the residual effect of sedation and/or paralysis
confounds the clinical examination.Q Electrophysiology:In patients who are comatose after
resuscitation from cardiac arrest and who are treated with targeted temperature management we
recommend using bilateral absence of N20 SSEP wave at .72h after ROSC to predict poor outcome. SSEP
recording requires appropriate skills and experience, and utmost care should be taken to avoid electrical
interference from muscle artefacts or from the ICU environment. In patients who are comatose after
resuscitation from cardiac arrest and who are treated with targeted temperature management we
suggest using EEG-based predictors such as absence of EEG reactivity to external stimuli, presence of
burst-suppression after rewarming or status epilepticus .72h after ROSC in combination with other
predictors for prognosticating a poor neurological outcome. We do not suggest using BIS to predict poor
outcome during TTM in patients who are comatose after resuscitation from cardiac arrest and are treated
with targeted temperature management. Qu: ??at the early pahse? Biomarkers:In patients who are
comatose after resuscitation from cardiac arrest and who are treated with targeted temperature
management we suggest using high serum values of NSE at 48 h-72 h from ROSC in combination with
other predictors for prognosticating a poor neurological outcome. However, no threshold enabling
prediction with zero FPR can be recommended. We also suggest using utmost care and preferably
sampling at multiple time-points when assessing NSE, to avoid false positive results due to haemolysis.
Imaging:In patients who are comatose after resuscitation from cardiac arrest and who are treated with
targeted temperature management we suggest using the presence of a marked reduction of the GM/WM
ratio on brain CT within 2 h after ROSC or the presence of extensive reduction in diffusion on brain MRI
at 2-6 days after ROSC in combination with other predictors for prognosticating a poor neurological
outcome. We suggest using brain imaging studies for prognostication only in centres where specific
experience is available.
CoSTR Attachments:
Evidence Profiles Table 3b TH.pdf

Evidence Profiles Table 3d TH.pdf
Evidence Profiles Table 3c TH.pdf
Sandroni Hypothermia TH plenary and TF.pdf
COSTR Draft Prognostication in Hypothermia 2015-3.pdf
Evidence Profile Table 3a TH.pdf
Prognostication in normothermia
Question Type:
Prognostic
Full Question:
Among adults who are comatose after cardiac arrest and are not treated with targeted temperature
management (P), does any clinical finding when normal (e.g. 1. Clinical exam 2. EEG 3. SSEP 4.Imaging
5. Other) (I), compared with any clinical finding when abnormal (C), change Survival with Favorable
Clinical examination: In patients who are comatose after resuscitation from cardiac arrest and who are
not treated with targeted temperature management, an absent pupillary reflex to light at 72h from ROSC
predicts poor outcome with high accuracy (0[0-8]% FPR). An absent corneal reflex at 72h from ROSC is
also an accurate predictor of poor outcome, but it is less specific (FPR 5[0-25]%). Sensitivity of
prediction is low (18-30%). The accuracy of the combined absence of pupillary and corneal reflexes is
equivalent to that of the absence of the pupillary reflex alone. An absent or extensor motor response to
pain (M2) within 72h from ROSC has a higher sensitivity than both pupillary and corneal reflexes for
prediction of poor outcome. However, its FPR is also higher (27[12-48]% at 48h and 15[5-31]% at 72h).
The prognostic accuracy of an M3 within 72h from ROSC is similar to that of M2. There is limited
evidence on the predictive value of Glasgow Coma Score. Moreover, this score represents a combination
of clinical signs, in which the role of the various components (eye, motor, or verbal responses) cannot be
evaluated separately. In patients who are comatose after resuscitation from cardiac arrest and who are
not treated with targeted temperature management presence of myoclonus or status myoclonus within
72h from ROSC predicts a poor outcome with high accuracy (0[0-5]% FPR). However, rare cases of good
outcome in patients with an early-onset myoclonus have been reported.48, 49 Blinding of the treating
team is very difficult to achieve for predictors based on clinical examination, which implies a risk of selffulfilling prophecy. Electrophysiology: In patients who are comatose after resuscitation from cardiac
arrest and who are not treated with targeted temperature management, a bilaterally absent N20 wave
within 72h from ROSC predicts a poor outcome with high precision (FPR from 0[0-3]% to 1[0-5]).
Conversely, a delayed or absent N70 SEP from 24h to 72h after ROSC is often associated to false
positive predictions. There is a potential risk of self-fulfilling prophecy for predictions based on absent
SSEP results. Unfavourable EEG patterns, such as EEG Grades 3-5 or 4-5, or an EEG below 21 V within
72h from ROSC, or a burst-suppression at 72h from ROSC predicted poor outcome with 0% FPR.
However, the definition of EEG grades was inconsistent among studies. The amplitude of the EEG signal
may be affected on a variety of technical conditions such as skin and scalp impedance, inter-electrode
distances, size, type and placement of the exploring electrodes, and type of filters adopted.51 Presence
of alpha coma during the first seven days from ROSC is only inconsistently associated with poor
outcome. Biomarkers: In patients who are comatose after resuscitation from cardiac arrest and who are
not treated with targeted temperature management, high concentrations of biomarkers predict a poor
outcome. However, the thresholds associated with 0% FPR vary between studies. S-100B is less well
documented than NSE. The main reasons for the observed variability in biomarkers thresholds include
the use of heterogeneous measurement techniques 53-55, the presence of extra-neuronal sources of
biomarkers (haemolysis and neuroendocrine tumors for NSE 56, muscle and adipose tissue breakdown
for S-100B 57), and the incomplete knowledge of the kinetics of their blood concentrations in the first
few days after ROSC. Advantages of biomarkers over other predictors such as EEG and clinical
examination include quantitative results and likely independence from the effects of sedatives. Imaging:
In patients who are comatose after resuscitation from cardiac arrest and who are not treated with
targeted temperature management the presence of global cerebral oedema or a reduction of the
grey/white matter interface, measured as the GWR within 48 hours from ROSC predicts an almost
invariably poor outcome. The GWR thresholds for 0% FPR vary among studies, according to the area
studied and the measurement technique adopted. The presence of diffuse hypoxic-ischemic injury
detected by DWI changes and quantified by ADC from 2 to 6 days from ROSC predicts poor outcome
with low FPR. The ADC thresholds for 0% FPR vary among studies, according to the cerebral area studied
and the measurement technique. All studies on prognostication after cardiac arrest using imaging have a
small sample size with a consequent very low precision, and are prone to selection bias.
Clinical examination: In patients who are comatose after resuscitation from cardiac arrest and who are
not treated with targeted temperature management, we recommend using the absence of pupillary
reflex to light (or the combined absence of both pupillary and corneal reflexes) at 72h from ROSC to
predict poor outcome. We do not suggest using an absent or extensor motor response to pain (M2)
alone to predict poor outcome in those patients, given its high false positive rate. However, due to its
high sensitivity, this sign may be used to identify the population with poor neurological status needing
prognostication or to predict poor outcome in combination with other more robust predictors. We suggest
using the presence of myoclonus or status myoclonus within 72h from ROSC in combination with other
predictors to predict poor outcome in comatose survivors of cardiac arrest. We suggest prolonging the
observation of clinical signs when interference from residual sedation or paralysis is suspected, so that
the possibility of obtaining false positive results is minimized. Electrophysiology: In patients who are
comatose after resuscitation from cardiac arrest and who are not treated with targeted temperature
management, we recommend using bilateral absence of the N20 SSEP wave within 72h from ROSC to
predict poor outcome. SSEP recording requires appropriate skills and experience, and utmost care should
be taken to avoid electrical interference from muscle artefacts or from the ICU environment. In patients
who are comatose after resuscitation from cardiac arrest and who are not treated with targeted
temperature management, we suggest using the presence of burst-suppression on EEG at 72h from
ROSC in combination with other predictors for prognosticating a poor neurological outcome. We do not
suggest using EEG grades due to the inconsistencies in their definitions. We also do not suggest using
low-voltage EEG given the potential interferences of technical factors on EEG amplitude. Biomarkers: In
patients who are comatose after resuscitation from cardiac arrest and who are treated with therapeutic
hypothermia we suggest using high serum values of NSE at 24 h-72 h from ROSC in combination with
other predictors for prognosticating a poor neurological outcome. However, no threshold enabling
prediction with zero FPR can be recommended. We also suggest using utmost care and preferably
sampling at multiple time-points when assessing NSE, to avoid false positive results due to haemolysis.
Imaging: In patients who are comatose after resuscitation from cardiac arrest and who are not treated
with targeted temperature management we suggest using the presence of a marked reduction of the
GM/WM ratio on brain CT within 48 h after ROSC or the presence of extensive reduction in diffusion on
brain MRI at 2-6 days after ROSC only in combination with other more established predictors for
prognosticating a poor neurological outcome. We also suggest using brain imaging studies for
prognostication only in centres where specific experience is available.
CoSTR Attachments:
Evidence Profile Table 3c NT.pdf
Evidence Profile Table 3b NT.pdf
COSTR Draft Prognostication in Normothermia 2015 - 2.pdf
ALS 713 Prognostication in non-TTM-treated Plenary and TF.pdf
Evidence Profile Table 3a NT.pdf
Evidence Profile Table 3d NT.pdf
Pulmonary embolism cardiac arrest

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest due to pulmonay embolism or suspected pulmonary embolism in
any setting (P), does any specific alteration in treatment algorithm (1. thrombolytics, 2. other) (I),
compared with standard care (according to 2010 treatment algorithm) (C), change Survival with
Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year,
Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?
Possible treatments for massive pulmonary embolism include administration of fibrinolytics, surgical
embolectomy and percutaneous mechanical thrombectomy. These therapies can also be considered
during cardiac arrest as a consequence of pulmonary embolism and have to be regarded separately.
Thrombolysis Data from non-randomized trials (Bttiger 1994, Krkciyan 2000, Lederer 2001, Bttiger
2001, Ruiz-Bailn 2001, Janata 2003, Lederer 2004, Stadlbauer 2006, Er 2009, Renard 2011, Dirican
2014), as well as reported outcome and follow-up of patients is very inhomogenous. Most retrospective
studies did not make subgroup analysis of patients with underlying PE. For the important outcome of
ROSC, Two studies that did subgroup analysis show beneficial results for the use of thrombolytic (TL)
drugs compared to controls (CON): ROSC was reported to be significantly higher in a retrospective
analysis (81.0% TL vs. 42.9% CON, P=0.03) (Krkciyan 2000; very low level of evidence; downgraded
for risk of bias). In a separate study, ROSC (66.7% in thrombolysis group vs. 43.3% in control group, RR
1.5 [CI 0.8-8.6])) was not different, but 24-h-survival (52.8% TL vs. 23.3% CON, RR 2.3 [CI 1.1-4.7])
showed favorable results for the use of thrombolytic drugs (Janata 2003; very low level of evidence,
downgraded for serious risk of bias). For the important outcome of survival to hospital discharge,
Hospital discharge rates were not different (9.5% TL vs 4.8% CON, N.S.) in a retrospective analysis
(Krkciyan 2000; very low level of evidence; downgraded for risk of bias). Hospital discharge (19.4% TL
vs. 6.7% CON, RR 2.9 [CI 0.75-13.8]) was not different with the use of thrombolytic drugs (Janata
2003; very low level of evidence, downgraded for serious risk of bias). For the critical outcome of
survival with good neurological status at 30, 90 or 180 days. There is only one randomized, controlled
trial comparing thrombolytics vs. placebo during cardiac arrest (Bttiger 2008). In this double-blinded
RCT (low level of evidence; downgraded for imprecision), 1050 patients were randomized to receive
either thrombolytic treatment (tenecteplase) or placebo during CPR; 37 of these patients had confirmed
pulmonary embolism as primary cause of cardiac arrest. However, this study was not powered to reach
significance in this small subgroup. Patients in whom PE was suspected were furthermore subject to use
of open label thrombolysis, and were not included in the trial at all. The 30 days survival in this subgroup
was not statistically different (p=0.31, RR 7.19 [95%CI 0.37-139.9]) between tenecteplase (2/15,
13.3%) vs. placebo (0/22, 0%). Two studies that had been included in the previous guidelines were
excluded, as the underlying condition for cardiac arrest (PE, myocardial infarction or others) was not
clear, and no analysis regarding the outcome between these subgroups was possible (Abu-Laban 2002,
Fatovich 2004). Surgical embolectomy For surgical embolectomy for cardiac arrest due to massive PE,
only two case series (Doerge 1996, Konstantinov 2007) were found by the search strategy and included
in further analysis. Survival of patients requiring surgical embolectomy during cardiopulmonary
resuscitation due to massive PE was 12.5% in a case series (Doerge 1996; very low level of evidence,
downgraded for risk of publication bias). Survival was reported to be higher (71.4%) in a more recently
published case series of 7 patients requiring surgical embolectomy during CPR due to massive PE
(Konstantinov 2007; very low level of evidence, downgraded for risk of publication bias). These results
do not offer any comparison for the routine use of surgical embolectomy for cardiac arrest due to
pulmonary embolism at this time. Percutaneous mechanical thrombectomy For percutaneous mechanical
thrombectomy, one case series (Fava 2005) was found by the search strategy and was included. ROSC
was achieved in 85.7% of all patients treated with percutaneous mechanical thrombectomy (very low
quality of evidence, downgraded for possible publication bias).
We suggest for the administration of thrombolytic agents for cardiac arrest when pulmonary embolism is
the suspected cause of cardiac arrest (weak recommendation, low level of evidence). We suggest for the
use of thrombolytic agents or surgical embolectomy or mechanical thrombectomy for cardiac arrest when
pulmonary embolism is the known cause of cardiac arrest PE (weak recommendation, low level of
evidence). We suggest against routine surgical embolectomy for cardiac arrest when pulmonary
embolism is the suspected cause of cardiac arrest (weak recommendation, very low level of evidence).
We suggest against routine use of mechanical thrombectomy for cardiac arrest when pulmonary
embolism is the suspected cause of cardiac arrest (weak recommendation, very low level of evidence).
Values and preferences statement: We acknowledge use of thrombolytic agents, surgical embolectomy
or mechanical thrombectomy, or combination for known pulmonary embolism in non-cardiac arrest
patients. We acknowledge the potential risk of bleeding after thrombolysis and choice of intervention
needs to take into account location, availability of interventions, and contraindications to thrombolysis.
CoSTR Attachments:
Percutaneous.pdf
RCT_Subgroup.pdf
SurgicalEmbolectomy.pdf
RCT_Gesamt.pdf
NonRCT_Gesamt.pdf
Steroids and hormones for cardiac arrest

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does corticosteroid or mineralocorticoid
administration during CPR (I), compared with not using steroids (C), change Survival with Favorable
For in-hospital cardiac arrests: For the important outcome of ROSC (return of spontaneous circulation)
there were 2 randomized control trials (Mentzelopoulos 2009,15 & 2013,270) of low quality evidence
(downgraded for indirectness and for imprecision) in 368 patients with in-hospital cardiac arrests. These
demonstrated an improved outcome with the use of methylprednisolone and vasopressin in addition to
epinephrine compared with the use of epinephrine and placebo. Mentzelopoulos 2009, found that ROSC
was higher in those treated with Vasopressin, Steroids (methylprednisolone) and Epinephrine +/hydrocortisone than in those treated with only epinephrine + placebo 39/48 (81.3%) vs 27/52 (51.9%,
p< 0.003). Mentzelopoulos 2013, found that ROSC was higher in those treated with Vasopressin,
Steroids (methylprednisolone) and Epinephrine +/- hydrocortisone than in those treated with only
epinephrine + placebo: 109/130 (83.9%) vs 91/138 (65.9%), OR 2.98 (95% CI 1.39-6.4, p = 0.005).
When the data were pooled, the overall OR for ROSC was 3.02 (95% CI 1.85-4.93). For the critical
outcome of survival to discharge, there was 1 randomized control trial (Mentzelopoulos 2009,15) of low
quality evidence (downgraded for indirectness and for imprecision) in 100 patients with in-hospital
cardiac arrest. This showed an improved outcome with the use of methylprednisolone + vasopressin +
epinephrine during cardiac arrest + hydrocortisone post-ROSC for those with shock, compared with the
use of only epinephrine and placebo (9/48 = 19% vs 2/52= 4%, p = 0.02). For the critical outcome of
survival to discharge with good neurological outcome, there was 1 randomized control trial
(Mentzelopoulos 2013,270) of low quality evidence (downgraded for indirectness and for imprecision) in
268 patients with in-hospital cardiac arrest. This demonstrated improved outcome with
methylprednisolone, vasopressin, epinephrine + hydrocortisone in those with post-ROSC shock
compared with those with only epinephrine + placebo [18/130 (13.9%) vs 7/138 (5.1%)], OR 3.28
(95% CI, 1.17 to 9.20; P = 0.02). For out-of-hospital cardiac arrest: For the important outcome of
ROSC, there were 2 studies (Paris 1984,1008, RCT & Tsai 2007, 318, observational study) of very low
quality in 183 patients. The RCT (Paris) demonstrated no improvement in ROSC with steroids in cardiac
arrest: 5.4% (2/37) with hydrocortisone achieved ROSC long enough to be admitted to ICU vs 8.7%
(4/46) who received placebo. However, the observational study (Tsai) demonstrated apparent benefit:
ROSC in 58% receiving hydrocortisone vs 38% without, p = 0.049. For out- of - hospital cardiac arrests,
for the critical outcome of survival to discharge, there were 2 studies (Paris 1984,1008 & Tsai 2007,
318) of very low quality in 183 patients. Both failed to show any benefit with the use of steroids: Paris
had no long-term survivors and Tsai demonstrated survival to discharge in 8% (3/36) receiving
hydrocortisone compared with 10% (6/61) receiving placebo, p = 0.805.
For IHCA: For IHCA we suggest that the combination of methylprednisolone, vasopressin & epinephrine
may be considered as an alternative to epinephrine alone during CPR (weak recommendation, low quality
evidence). Values and preferences statement: Mortality is high and there are few interventions known to
improve outcome from in hospital cardiac arrest, so it is reasonable to consider the use of the tripleagent drug regime since it would be relatively easy to implement and of low cost. However, a larger,
multi-centre randomized control trial to further assess the effect of the use of steroids in cardiac arrest,
both in combination with vasospressin & epinephrine and with epinephrine alone would be useful. For
OHCA: We recommend against the routine use of steroids during CPR for OOHCA. Values and preference
statement: There is very little evidence of poor quality from two studies regarding the effect of the
addition of a dose of steroids during out-of-hospital cardiac arrest, but both studies demonstrated no
benefit, so the cost of their addition doesnt seem worthwhile.
CoSTR Attachments:
Summary of Bias Assessments for Use of Steroids in Cardiac Arrest.xlsx
Characteristics of the 2 Studies by Mentzelopoulos 2009+ 13 for AMSTAR.docx
GradePro table for Steroids during CPR for OHCA.docx
R ROSC Forest plot.svg
GradePro table for Steroids during CPR for IHCA.docx
AMSTARguidelineTool.pdf
Final Article selection for Steroids in CA.xlsx
Steroids in CA - ILCORSlideTemplate.Dallas2015.plenary and TF. 1.7.15.ppt
Observational Studies on smoking in pregnanch; GradePro.docx
Timing of drug delivery (epinephrine)

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does early epinephrine delivery (e.g. less than
10 minutes after the beginning of resuscitation by IV or IO route) (I), compared with delayed timing
epinephrine delivery (e.g. more than 10 minutes after the beginning of resuscitation) (C), change
AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?
For In-Hospital Cardiac Arrests For in-hospital cardiac arrests, for the critical outcome of survival to
hospital discharge, there was one observational study (Donnino 2014, g3028) of low quality
(downgraded for serious risk of bias and upgraded for dose-response effect) in 25,905 in-hospitalcardiac arrests with a non-shockable rhythm, that demonstrated an improved outcome with early
administration of adrenaline : Adjusted OR compared with reference interval of 1-3 min of 0.91 (95% CI
0.82 - 1.00) when given after 4-6 mins , 0.74 (95% CI 0.63 - 0.88) when given after 7-9 mins and 0.63
(95% CI 0.52 - 0.76) when given at > 9 mins after onset of arrest. For in-hospital cardiac arrests, for
the critical outcome of neurologically intact survival at hospital discharge (assessed with CPC 2), there
was one observational study (Donnino 2014,g3028) of low quality (downgraded for serious risk of bias
and upgraded for dose-response effect) in 25,905 in-hospital cardiac arrests with a non-shockable
rhythm, that demonstrated an improved outcome from early administration of adrenaline: Adjusted OR
compared with reference interval of 1-3 min of 0.93 (95% CI 0.82 - 1.06) when given after 4-7 mins,
0.77 (95% CI 0.62 - 0.95) when given after 7-9 mins and 0.68 (95% CI 0.53 - 0.86) when given at > 9
mins after onset of arrest. For in-hospital cardiac arrests, for the important outcome of return of
spontaneous circulation (ROSC), there was one observational study (Donnino 2014, g3028) of low
quality (downgraded for serious risk of bias and upgraded for dose-response effect) in 25,905 inhospital- cardiac arrests with a non-shockable rhythm, that demonstrated an improved outcome from
early administration of adrenaline: Adjusted OR compared with reference interval of 1-3 min of 0.90
(95% CI 0.85 - 0.94) when given after 4-7 mins, 0.81 (95% CI 0.74 - 0.89) when given after 7-9 mins
and 0.70 (95% 0.61 - 0.75) when given at > 9 mins. No studies were identified that looked specifically
at the effect of timing on administration of epinephrine after IHCA with shockable rhythms.
========= For OOHCA For the critical outcome of survival to hospital discharge, there were four
observational studies (Goto 2013,R188, Nakahara 2013,782, Koscik 2013,915 and Stielle 1992,1045) of
very low quality evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision) ,
enrolling over 420,000 OOHCAs that did not demonstrate any consistent benefit from early
administration of adrenaline : One study enrolling 209,577 OOHCAs (Goto 2013,R188) demonstrated no
significant difference in one month survival for shockable rhythms when epinephrine was administered
pre-hospital in < 9min (OR 0.95; 95% CI, 0.771.16), but a negative association was observed with prehospital epinephrine administration at > 10 min - OR 0.51 (95% CI, 0.44 0.59 for epinephrine given at
10-19 min post arrest, and OR 0.33 (95% CI 0.250.4 for epinephrine given at > 20min post arrest).
However, for non-shockable rhythms early pre-hospital epinephrine was associated with an improved
outcome (one month survival): pre-hospital epinephrine at < 9min OR = 1.78 (95% CI 1.5-2.1) /
epinephrine at 10-19min = OR of 1.29 (95% CI 1.17-1.43) / epinephrine at > 20 min = OR of 0.79
(95% CI 0.66-0.93). Another study enrolling 212,228 OOHCAs (Nakahara, 2013, 782) showed improved
outcome (survival) for arrests of cardiac origin, with early pre-hospital epinephrine (< 0.001). Similarly,
for arrests of non-cardiac origin, early pre-hospital epinephrine (< 0.001). This benefit held when MVLRA
was done with the primary predictor the total time from call to administration of epinephrine - for arrests
of cardiac origin and non-cardiac origin, early pre-hospital epinephrine ( 10 mins - OR 0.91 (95% CI
0.35, 2.37; C-statistic 0.75). However, for PEA, OR 2.35 (95% CI 0.38 -14.7, p = 0.32) for survival with
early epinephrine (at < 10mins) compared with epinephrine at > 10 mins. However, for VF early
epinephrine was not associated with any significant beneficial effect OR = 1.52 (95% CI 0.53- 4.40,
p=0.41) for survival with early epinephrine (at < 10mins) compared with epinephrine at > 10 mins. For
the critical outcome of neurologically intact survival at hospital discharge (assessed with CPC 2), there
were three observational studies (Goto 2013,R188, Hayashi 2012,1639 & Nakahara 2012,782) of very
low quality evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision and
upgraded for a stong association) involving over 261,000 out-of-hospital cardiac arrests that
demonstrated variable benefit from early administration of early epinephrine: One study enrolling
209,577 OOHCAs (Goto 2013, R188) did not show any significant difference in one month CPC 1-2 for
shockable rhythms or non-shockable rhythms with pre-hospital epinephrine administered in < 9 min
[aOR 0.71 (95% CI = 0.54-0.92) & 0.95 (0.62-1.37)] compared with no pre-hospital epinephrine.
However, there was a negative association for one month CPC 1-2 with pre-hospital epinephrine given at
>10 min: For shockable rhythms with pre-hospital epinephrine at 10-19 min OR= 0.34 (95% CI=0.28-
0.42) & with pre-hospital epinephrine at > 20min OR = 0.21 (95% CI=0.14-0.31); For non-shockable
rhythms OR 0.63 (95% CI = 0.48-0.80) & 0.49 (95% CI = 0.32-0.71) for pre-hospital epinephrine
administered at 10-19 and > 20 minutes after arrest. In one study enrolling 3,161 subjects (Hayashi
2012,1639), in VF/VT early pre-hospital epinephrine (at 10min from EMS receipt of call to
administration of epinephrine) was associated with improved 1 month neurological outcome compared
with no pre-hospital epinephrine, with a big effect size (OR 6.34 (95% CI 1.49-27.02)), However, later
epinephrine was associated with a worse outcome epinephrine at 11-20 min aOR 0.65 (95% CI 0.361.20) and epinephrine at 21min aOR 0.19 (95% CI 0.08-0.47). In the non-VF group, none received
early epinephrine, but later epinephrine was associated with a worse neurological outcome: aOR 0.61
(95% CI 0.26-1.44 ) for CPC of 1-2 at 1 month in those with epinephrine at 11-20mins compared with
no epinephrine, and for epinephrine at 21min aOR 0.51 (95% CI 0.22-1.22). In another study enrolling
over 49,000 cases (Nakahara 2013,782), for arrests of cardiac origin and non-cardiac origin, early prehospital epinephrine (10mins). Another study enrolling 209 577 OOHCAs (Goto), showed that prehospital epinephrine administration at < 9 min after arrest, was positively associated with ROSC for
non-shockable rhythms aOR for ROSC was 8.83 (95% CI 8.01-9.73), and for shockable rhythms, OR was
1.45 (95% CI 1.201.75). For non-shockable rhythms, there was also a positive association for prehospital epinephrine given at 10-19 & > 20 mins after arrest: OR 6.18 (95% CI 5.82-6.56) & 4.32 (95%
CI 3.98-4.69). However, for shockable rhythms, there was a negative association between ROSC & prehospital epinephrine given at 10-19 & > 20 mins after arrest (OR 0.88, CI 0.78-1 / 0.63, 0.52-0.77).
Another observational study enrolling 686 OOHCAs (Koscik 2013, 915) showed that overall, early
epinephrine (10mins after 911 call) with aOR for ROSC of 1.78 (1.15,2.74; C-statistic 0.63). For
witnessed arrests, early epinephrine was also associated with improved ROSC - aOR 3.20 (1.75,5.88; C
statistic 0.68)] and for PEA, early epinephrine was associated with improved ROSC, OR 3.45 (1.56,7.62).
However, for VF/VT early epinephrine was not associated with significant improvement in ROSC [OR 1.66
(0.83, 3.31)].
For In and Out of HCA with an initial non-shockable rhythm, we suggest that if epinephrine is to be
administered, it is given as soon as feasible after the onset of the arrest (weak recommendation, low
quality evidence). Values and preferences statement: In making this recommendation, we place a high
value on being able to modify a current (standard) treatment at minimal cost. For IHCA with an initial
shockable rhythm we found insufficient data to make a treatment suggestion regarding the timing of
administration of epinephrine (there were no studies addressing this issue). For In and Out of HCA with
an initial shockable rhythm, we found insufficient evidence to make a treatment suggestion regarding the
timing of administration of epinephrine, particularly in relation to defibrillation, and the optimal timing
may vary for different groups of patients and different circumstances. Values and preferences statement:
Thought there is insufficient evidence to support a treatment recommendation, we place a higher value
on early defibrillation than on administration of epinephrine.
CoSTR Attachments:
R2 Joint CoStar Statement Dec 2014 .docx
Time to Epi. GRADE and study overview IHCA.pdf
Summary of Bias Assessments Example and Template.xlsx
Timing of Adminstration of Epinephrine GradePro table Jan 2015.docx
Ultrasound during CPR

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does use of ultrasound (including
echocardiography or other organ assessments) during CPR (I), compared with standard CPR and
resuscitation without use of ultrasound (C), change Survival with Favorable neurological/functional
For the important outcome of ROSC, we identified one randomized controlled trial investigating the use
of cardiac ultrasound use during ACLS, compared to no use of cardiac ultrasound during ACLS in adult
patients with PEA arrest.[Chardoli;2012;287] This study enrolled 100 patients in a convenience sample
and reported ROSC for at least 10 seconds in 34% of patients in the US group vs 28% in the group with
no US (p=0.52). The evidence was downgraded for imprecision (small sample size), and very high risk of
bias (no information anout randomization allocation, lack of blinding, lack of blinding in outcome
assessors). This evidence was therefore graded as very low quality. For the critical outcome of survival,
we identified one observational study.[Prosen;2010;1548] The evidence was downgraded for very high
risk of bias (significant confounding, selection bias) and imprecision (small sample size). Therefore we
concluded that the data does not provide enough evidence to address the PICO question.
There is inadequate evidence to evaluate the benefit of cardiac US during ACLS. Based on expert
opinion, we suggest (weak recommendation, very low quality evidence) that if a qualified sonographer is
present and cardiac US can be performed without interfering with standard ACLS protocol, it may be
considered as an additional diagnostic tool to identify potentially reversible causes.
CoSTR Attachments:
US.PICO.Presentation.ppt
Vasopressors for cardiac arrest (1. Epi v Placebo)

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does does use of epinephrine (I), compared
with placebo or not using epinephrine (C), change Survival with Favorable neurological/functional
For all four long term (critical) and short term (important) outcomes, we found one underpowered trial
that provided low quality evidence comparing SDE to placebo (Jacobs, 2001, 1138). Among 534
subjects, there was uncertain benefit or harm of SDE over placebo for the critical outcomes of survival to
discharge [RR 2.12, 95% CI 0.75-6.02, p=0.16] and good neurological outcome defined as CPC of 1-2
[RR 1.73, 95% CI 0.59-5.11, p=0.32]. However, patients who received SDE had higher rates of the two
important outcomes of survival to admission [RR 1.95, 95% CI, 1.34-2.84, p=0.0004] and ROSC in the
prehospital setting [RR 2.80, 95% CI 1.78-4.41, p
Treatment Recommendation Given the observed benefit in short term outcomes, we suggest Standard
Dose Epinephrine be administered to patients in cardiac arrest.(weak recommendation, low quality)
Values and Preferences Statement: In making this statement, we place value on the short-term
outcomes of ROSC and survival to admission, and our uncertainty about the absolute effect on survival
and neurological outcome.
CoSTR Attachments:
C2015_Worksheet_ALS_Vasopressors in cardiac arrest Jan 2 2015.docx
Epi vs. Placebo.docx
Vasopressors for cardiac arrest (2. Epi vs. high dose Epi)
Question Type:
Intervention
Full Question:
In adult patients in cardiac arrest in any setting (P), does high dose epinephrine (at least 0.2 mg/kg or
5mg bolus dose) (I), compared with standard dose epineprine (1mg bolus dose) (C), change survival to
180 days with good neurological outcome, survival to 180 days, survival to hospital discharge with good
neurological outcome, survival to hospital discharge, ROSC (O)?
All of these trials have been uniformly downgraded for indirectness by the TF due to the age of the trials
Despite the high quality evidence that HDE improves short term outcomes we recommend against the
routine use of HDE in cardiac arrest treatment.(strong, moderate quality) Values and Preferences
Statement: In making this statement, we noted that multiple high and moderate quality trials failed to
demonstrate an improvement the critical outcomes of survival and neurological outcome. The absolute
magnitude of effects of HDE vs. SDE on ROSC are much less than the difference in SDE vs. Placebo.
These HDE studies were performed in the 1990s since when care and outcomes have changed
dramatically, making it hard to interpret the relevance of these results when compared with current care.
CoSTR Attachments:
SDE vs. HDE.docx
Vasopressors for cardiac arrest (3. Epi vs. Vasopressin)

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does use of epinephrine (I), compared with
vasopressin (C), change survival to 30 days with good neurological outcome, survival to 30 days, survival
to hospital discharge with good neurological outcome, survival to hospital discharge, ROSC (O)?
We found a single RCT (Mukoyama 2009; 755) n=336 that compared multiple doses of Standard Dose
Epinephrine (SDE) with multiple doses of Standard Dose Vasopressin in the Emergency Department after
OHCA. The trial had a high rate of bias as much of the methodology is unclear and there was a 37% post
randomization exclusion. The primary outcome measure was CPC score of 1 or 2 however neither the
sample size estimate nor power calculation were included in the paper. There were no significant
differences in either critical outcomes of survival to discharge with neurological outcome as defined as
Cerebral Category Performance Score of 1 or 2 (RR 0.68, 95% CI 0.251.82, p = 0.44) or survival to
discharge (RR 0.68, 95% CI 0.251.82, p = 0.44) or the important outcome of ROSC (RR 0.93, 95% CI
0.661.31, p = 0.67).
Treatment Recommendation: We suggest against initiating vasopressin as a substitution for epinephrine
in the treatment in cardiac arrest. (weak recommendation, low quality) Values and Preferences
Statement: The recommendation considers the fact that vasopressin is widely used now, and the
available data do not indicate any reason to change practice.
CoSTR Attachments:
Epi vs. Vasopressin.docx
Vasopressors for cardiac arrest (4. Epi vs. Epi/Vaso)

Question Type:
Intervention
Full Question:
Among adults who are in cardiac arrest in any setting (P), does use of both vasopressin and
epinephrine (I), compared with using epinephrine alone (C), change Survival with Favorable
For the critical outcome of survival to hospital discharge with CPC of 1 or 2 we found 3 RCTs
(Gueugniaud 2008, 21; Ong 2012, 953; Wenzel 2004, 105 moderate quality) N=2402 comparing
standard dose epinephrine (SDE) with vasopressin epinephrine combination therapy demonstrated no
superiority with vasopressin epinephrine combination (RR of 1.32 95% CI of 0.88 and 1.98). For the
critical outcome of survival to hospital discharge we found 5 RCTs (Ducros, 2011, 453; Gueugniaud
2008, 21; Lindner 1997, 535;Ong 2012, 953; Wenzel 2004, 105 moderate quality) n=2438 comparing
SDE to vasopressin and epinephrine combination therapy did not demonstrate superiority with
vasopressin and epinephrine combination therapy in survival to discharge [RR 1.12, 95% CI 0.84-1.49,
p=0.45] For the important outcomes of survival to admission we found 5 RCTs (Ducros, 2011, 453;
Gueugniaud 2008, 21; Lindner 1997, 535;Ong 2012, 953; Wenzel 2004, 105 high quality) n=2438
demonstrating no significant differences in survival to hospital admission with vasopressin epinephrine
combination therapy (0.88, 95% CI 0.73-1.06, p=0.17) For the important outcomes of return of
spontaneous circulation (ROSC) we found 6 RCTs (Callaway 2006, 1316; Ducros, 2011, 453; Gueugniaud
2008, 21; Lindner 1997, 535;Ong 2012, 953; Wenzel 2004, 105 high quality) demonstrating no ROSC
advantage with vasopressin epinephrine combination therapy with RR 0.96, 95% CI 0.89-1.04, p=0.31.
We suggest against adding vasopressin to standard dose epinephrine during cardiac arrest. (weak
recommendation, moderate quality) Values and Preferences Statement: In making this recommendation,
we considered it distracting and costly to add a drug that has no evidence of additional benefit for
patients. We also have no reason to withdraw this drug if the drug is currently in use.
CoSTR Attachments:
Epi vs. Epi Vaso Combo.docx
Ventilation rate during continuous chest compression

Question Type:
Intervention
Full Question:
in adults with cardiac arrest with a secure airway receiving chest compressions (in any setting, and with
standard tidal volume) (P), does does a ventilation rate of 10 breaths/min (I), compared with compared
to any other ventilation rate (C), change Survival with Favorable neurological/functional outcome at
discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180
days AND/OR 1 year, ROSC (O)?
We did not identify any evidence to address the critical outcomes of Survival with favorable
neurological/functional outcome at discharge, 30 days, 60 days, 180 days and, or 1 year Survival at
discharge, 30 days, 60 days, 180 days AND/OR 1 year. We identified very low quality evidence
(downgraded for very serious risk of bias and indirectness, and serious inconsistency and imprecision)
from 10 animal studies [Sanders 2002 553, Aufderheide 2004 s345, Aufderheide 2004 1960,
Yannopoulos 2004 75, Yannopoulos 2006 1444, Hayes 2007 357, Cavus 2008 118, Hwang 2008 183,
Gazmuri 2012 259, Kill 2014 e89] and 1 human non-RCT [Abella 2005 305] that does not enable us to
estimate the effect of a ventilation rate of 10 per minute compared to any other rate for the important
outcome of ROSC with confidence.
We suggest a ventilation rate of 10 breaths per minute in adults with cardiac arrest with a secure airway
receiving continuous chest compressions (weak recommendation, very low quality evidence)
CoSTR Attachments:
Ventilation Rate after ROSC_3Jan2015.docx
ALS808_VentilationduringContinousCCILCORSlides_14Dec2014.pptx
Ventilation strategy post resuscitation

Question Type:
Intervention
Full Question:
Among adults with ROSC after cardiac arrest in any setting (P), does ventilation to a specific pCO2 or pO2
goal (I), compared with 1. no specific strategy or 2. a different pCO2 or pO2 goal (C), change Survival
only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival with Favorable
neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year (O)?
Hypocapnia No studies have specifically randomised patients to ventilation to a specific PaCO2 goal. For
the critical outcome of neurologically intact survival, two very low quality cohort studies {Roberts 2013
2107, Lee 2014 55} with a total of 8,376 patients (downgraded for very serious concerns about risk of
bias and imprecision) showed hypocapnia (PaCO2 6.7kPa) One very low quality cohort study {Lee 2014
2107} with a total of 850 patients (downgraded for very serious concerns about risk of bias and
imprecision) showed no difference in outcome for patients ventilated to hypercapnia (>PaCO2 6.0kPa).
One very low quality cohort study {Verhaasalo 2014 1463} with a total of 409 patients (downgraded for
very serious concerns about risk of bias and imprecision) showed better outcome for patients ventilated
to hypercapnia (PaCO2 5.1-10.1 kPa). For the critical outcome of of death (or failure to be discharged
home), One very low quality cohort study {Schneider 2013 927} with a total of 16,542 patients
(downgraded for very serious concerns about risk of bias and imprecision) showed no difference in
patients ventilated to hypercapnia (PaCO2 >6.0kPa) One very low quality cohort study {Lee 2014 2107}
with a total of 850 patients (downgraded for very serious concerns about risk of bias and imprecision)
showed a higher mean PaCO2 in survivors.
No studies demonstrate better outcome with ventilation to a specific PaCO2 in patients with ROSC. We
suggest maintaining PaCO2 within a normal physiological range as part of a post-ROSC bundle of care
(weak recommendation, very low quality evidence). No studies demonstrate better outcome with
ventilation to a specific PaCO2 in patients with ROSC. Hypocarbia is associated with worse outcome and
we suggest should be avoided where possible (moderate recommendation, very low quality evidence).
The upper limit at which PaCO2 becomes harmful is unknown, although mild hypercapnia may have
some neuroprotective effect (weak recommendation, very low quality evidence).
CoSTR Attachments:
ILCOR ALS571-post review.ppt
ILCOR ALS571-post review Final.ppt
ILCOR ALS571-post review Final.pdf
ALS 571 Ventilation to a specific pCO2 or pO2 goal.docx

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Advanced airway placement (ETT vs SGA)

Airway placement (Basic vs Advanced)

Antiarrhythmic drugs for cardiac arrest

ALS 428 should-amiodarone-vs-placebo-be-used-for-adults-who-are-in-cardiac-arrest-in-anysetting.pdf

Antiarrhythmic drugs post resuscitation

Cardiac arrest during PCI

eCPR vs manual CPR

ETCO2 to predict outcome of cardiac arrest

Exhaled CO2 detection and esophageal detection devices

Fever after cardiac arrest

Glucose control following resuscitation

Hemodynamic support post resuscitation

Impedance threshold device

Induced Hypothermia (duration)

Induced Hypothermia (timing)

Lipid Therapy for Cardiac Arrest

Mechanical CPR Devices

Oxygen dose after ROSC in adults

Oxygen dose during CPR

Pregnancy and cardiac arrest

Evidence Profiles Table 3b TH.pdf

Pulmonary embolism cardiac arrest

Steroids and hormones for cardiac arrest

Timing of drug delivery (epinephrine)

Ultrasound during CPR

Vasopressors for cardiac arrest (1. Epi v Placebo)

Vasopressors for cardiac arrest (3. Epi vs. Vasopressin)

Vasopressors for cardiac arrest (4. Epi vs. Epi/Vaso)

Ventilation rate during continuous chest compression

Ventilation strategy post resuscitation

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