Ilcor 2015 Sva

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

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]
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
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(weak recommendation, very low quality evidence) for in hospital cardiac arrest.
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)

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)

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.
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
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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).
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.
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
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
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)
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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) <90 mm
Hg was associated with higher mortality (65% vs 37%) and diminished discharge functional status in survivors (49% vs
38%). Trzeciak (2009, 2895)
For the critical outcome of survival we have identified very low quality evidence (downgraded for risks of bias and
publication bias) from two retrospective single centre studies including 2282 patients that showed reduced survival for
patients with post ROSC SBP <90 mm Hg (Bray 2014, 509) and <100 mm Hg (Kilgannon 2008, 410).
2. Does a bundle of therapies including a specific blood pressure target compared to no bundle
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 seven studies including 813 patients:
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 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 <75 mm Hg was a threshold for intervention showed no difference in
neurological outcome at hospital discharge (Laurent 2002, 2110).
One retrospective study of 136 patients identified groups with 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<.01)
(Mullner 1996, 59).
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). 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, 1.34–12.66; 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 post-resuscitation 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).
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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).
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 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)?
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-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 1.28 (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
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-of-hospital cardiac arrests that were unable to
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 preferences statement: In making this recommendation we place a higher value
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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 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 preferences statement: In making this recommendation
we place a higher value on not allocating resources to an intervention with equivocal benefit for critical or important
outcomes.
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-
34ºC) (I), compared with normothermia (36-37ºC) (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)?
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 moderate
quality evidence from one randomized control trial (RCT) [1] and one pseudorandomized trial [2] 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,” moderate 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),1 while the other study found no significant difference
(51% vs 68% hospital mortality, p=0.145).2 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].[3-5] 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 (adjusted OR 1.44 [95% CI, 1.039-2.006].[6] This data was not pooled with the above studies due to
the lack of temperature data and limited patient information available. 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.[4]In-
hospital cardiac arrest: We found no RCT’s 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).[7] 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 high 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).[8] 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.[9] This study found no benefit (neurologically intact survival 44.4% vs 11.1%, p=0.12), although with only 36
patients it was underpowered. [1] The Hypothermia After Cardiac Arrest Study Group,2002;549. [2] Bernard;2002;
557.[3] Dumas; 2011; 877.[4] Testori;2011;1162.[5]Vaahersalo;826; 2013. [6] Mader;2014;21.[7] Nichol;2013;620. [8]
Nielsen;2013;2197. [9] Lopez-de-sa;2012;2826.
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).
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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 32°C and 36°C 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.
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 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)?
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 very low 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
in-hospital 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) . Four studies (Dickinson 1998 289, Halperin 1993 762, Lu
2010 496, Wik 2014 741) (n=4,432) demonstrated benefit with mechanical chest compression devices, however
methodology of the Wik study did not allow 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:
7
In making this recommendation we place value on data from a large, high-quality RCT demonstrating equivalence between
high quality manual chest compressions and manual 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.
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 (Mateos-Rodriguez 2012)
For the critical outcome of immediate graft survival, 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 (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).
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).
8
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.
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 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 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
9
124/1156 vs. 245/1171 [29 vs. 38%], unadjusted OR 0.45 [95%CI 0.36 -0.58] P<0.0001).
• Bellomo [2011 R90] reported no difference in discharge to home [hyperoxia vs. normoxia (27 vs. 34%) - effect size
cannot be estimated from data]
Survival to hospital discharge (or survival to 30 days):

[7 observational studies, Kilgannon 2010 2165, Kilgannon 2011 2717, Bellomo 2011 R90, Janz 2012 3135, Ihle 2013 186,
Nelskyla 2013, Elmer 2014]
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 inconsistency, indirectness, confounding) from 7 observational studies with
conflicting results [4 showed hyperoxia worse than normoxia].
• Kilgannon [2010 2165] showed a worse outcome with hyperoxia vs. normoxia based on the first ICU PaO2 (in-hospital
mortality 63 vs. 45%, adjusted OR hyperoxia exposure 1.8 [95% CI 1.5-2.2 P = 0 .001]).
• Kilgannon [2011 2717] showed a 100 mm Hg increase in PaO2 was associated with a 24% increase in mortality risk
(odds ratio 1.24 [95% confidence interval 1.18 to 1.31]).
• Bellomo [2011 R90] showed no association between hyperoxia vs. normoxia (based on the worse PaO2 in first 24 h on
ICU) adjusted OR for hospital mortality of 1.2 (95% CI 1.0 to 1.5) P= 0.04).
• 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. Survivors had lower maximum PaO2
(198 mm Hg; interquartile range, 152.5–282) vs. non survivors (254 mm Hg; interquartile range, 172–363; p =0.022).
Adjusted OR - higher PaO2 increased in-hospital mortality (odds ratio 1.439; 95% CI 1.028–2.015; P = .034).
• 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 (hospital mortality 47 vs. 41%, adjusted OR hyperoxia vs. normoxia 1.2 [95%CI 0.51 -2.82]).
• Nelskyla [2013] enrolling 122 ICU admissions patients that showed no difference between patients with hyperoxia (PaO2
> 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).
10
• 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).
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:
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:
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
11
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:
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.
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.Qü
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.
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.
Prognostication in normothermia
12
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 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 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 (M≤2) 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 M≤3 within 72h from ROSC is similar to that of M≤2.
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.
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
self-fulfilling prophecy.
Electrophysiology:
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 µV 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:
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:
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.
13
Clinical examination:
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 (M≤2) 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:
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.
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:
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.
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 (Böttiger 1994, Kürkciyan 2000, Lederer 2001, Böttiger 2001, Ruiz-Bailén 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)
(Kürkciyan 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,
14
Hospital discharge rates were not different (9.5% TL vs 4.8% CON, N.S.) in a retrospective analysis (Kürkciyan 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 (Böttiger 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.
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 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)?
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) of low quality (downgraded for serious risk of bias and upgraded for dose-response effect) in 25,905 in-
15
hospital- cardiac 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) 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) 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 0.90 (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 OOHCA with
PEA.
=========
For OOHCA
For the critical outcome of survival to hospital discharge, there were four observational studies (Goto, Nakahara , Koscik
(2013) and Stielle (1992)) of very low quality evidence, enrolling over 420,000 OOHCAs that did not demonstrate any
consistent benefit from early administration of adrenaline : One study enrolling 209,577 OOHCAs (Goto) demonstrated no
significant difference in one month survival for shockable rhythms when epinephrine was administered pre-hospital in <
9min (OR 0.95; 95% CI, 0.77–1.16), but a negative association was observed with pre-hospital 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 0.25–
0.4 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) showed improved outcome (survival) for arrests of cardiac origin,
with early pre-hospital epinephrine (<10min from EMS CPR) compared with no pre-hospital epinephrine, OR = 1.73 (95%
CI = 1.46 to 2.04, p =< 0.001). Similarly, for arrests of non-cardiac origin, early pre-hospital epinephrine (<10min from
EMS CPR) showed improved outcome (survival) compared with no pre-hospital epinephrine, OR = 1.89 (95% CI = 1.37 to
2.61, p value of < 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
(<17min) was associated with improved outcome (survival) compared with no pre-hospital epinephrine, OR = 1.94 (95%
CI =1.65 to 2.28) and 2.00 (95% CI = 1.45 to 2.77) respectively.
Another study enrolling 686 OOHCAs (Koscik) did not demonstrate any overall improved survival to discharge with early
epinephrine (at <10mins) compared with epinephrine at > 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, Hayashi & Nakahara (2012)) of very low quality evidence 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) 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), 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 0.36-1.20) 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), for arrests of cardiac origin and non-cardiac origin, early pre-
16
hospital epinephrine (<10min from EMS initiated CPR) was associated with a higher rate of intact neurological survival
(aOR = 1.39, 95% CI = 1.08 to 1.78), p = 0.01 and OR = 2.01 (95% CI = 0.96 to 4.22), though this wasn’t significant as
p = 0.06). With the primary predictor the total time from call to administration of epinephrine, for cardiac origin & none
cardiac origin OHCA, early pre-hospital epinephrine (<17min) was still associated with a higher rate of intact neurological
survival than without, aOR = 1.70 (95% CI = 1.34 to 2.15) & 2.20 ( 95% CI = 1.05 to 4.60) respectively.
For the important outcome of ROSC, there were four observational studies (Cantrell, Goto & Koscik 2013, Stielle 1992) of
very low quality evidence in over 210,000 out-of-hospital cardiac arrests that demonstrated a benefit from early
administration of adrenaline: One study (Cantrell) enrolling 360,OOHCAs showed that patients receiving the first
vasopressor dose (either epinephrine or vasopressin) within 10 minutes after EMS call receipt were twice as likely to
experience ROSC (OR 1.91, 95% confidence interval [CI] = 1.01–3.63,p = 0.04) in comparison with those receiving it late
(>10mins). Another study enrolling 209 577 OOHCAs (Goto), showed that pre-hospital 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 1.20–1.75). For non-shockable rhythms, there was also a
positive association for pre-hospital 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 & pre-hospital
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) showed that overall, early epinephrine (<10 mins after EMS
call) was associated with improved ROSC vs late 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.
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 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)?
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<0.00001] compared to those who received placebo.
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)

In making this statement, we place value on the short-term outcomes of ROSC and survival to admission, and our
17
uncertainty about the absolute effect on survival and neurological outcome.
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 <1999.
For the critical outcome of survival to hospital discharge with a good CPC score of 1 or 2 we found 2 RCTs comparing
standard dose epinephrine (SDE) with high dose epinephrine (HDE) (Callaham 1992, 2667; Gueugniaud 1998, 1595 low
quality) n=1920 and cumulative relative risk (RR) did not demonstrate any survival to discharge with a good CPC score
advantage with HDE with a RR of 1.2 95% CI of 0.74, 1.96.
For the critical outcome of survival to hospital discharge we found 5 RCTs comparing standard dose epinephrine (SDE)
with high dose epinephrine (HDE) (Brown 1992, 1051; Callaham 1992, 2667; Gueugniaud 1998, 1595; Sherman 1997,
242; Stiell 1992, 1045; low quality) n=2859 and cumulative RR did not demonstrate any survival to discharge advantage
with HDE with a RR of 0.97 with 95% CI of 0.71, 1.32.
For the important outcome of survival to hospital admission we found 4 RCTs comparing SDE with HDE (Brown 1992,
1051; Callaham 1992, 2667; Gueugniaud 1998, 1595;Choux 1995,3; Moderate quality) n=2882 and the cumulative RR
demonstrated a survival to hospital admission advantage with HDE with a RR of 1.15 with 95% CI of 1.0, 1.32.
For the important outcome of return of spontaneous circulation (ROSC) we found 6 RCTS comparing SDE with HDE (Brown
1992, 1051; Callaham 1992, 2667; Choux 1995, 3; Gueugniaud 1998, 1595; Sherman 1997, 242; Stiell 1992, 1045;
Moderate quality) n=3130 and the cumulative RR demonstrated a ROSC advantage with HDE with a RR of 1.17 (95% CI
1.03, 1.34)
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 1990’s since when care and outcomes have changed dramatically, making it hard to interpret the
relevance of these results when compared with current care.
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
18
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 0.25–1.82, p = 0.44) or survival to
discharge (RR 0.68, 95% CI 0.25–1.82, p = 0.44) or the important outcome of ROSC (RR 0.93, 95% CI 0.66–1.31, p =
0.67).
We suggest against initiating vasopressin as a substitution for epinephrine in the treatment in cardiac arrest. (weak
recommendation, low quality)

The recommendation considers the fact that vasopressin is widely used now, and the available data do not indicate any
reason to change practice.
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 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)?
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.
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)?
19
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)
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 (<3.0 kPa & <4.7kPa respectively) was associated with a worse outcome.
For the critical outcome of death (or failure to be discharged home), one very low quality cohort study {Schneider 2013
927} of 6,881 patients (downgraded for very serious concerns about risk of bias and imprecision) showed hypocapnia
(<4.7kPa) was associated with a worse outcome.
Hypercapnia
No studies have specifically randomised patients to ventilation to a specific PaCO2 goal.
For the critical outcome of neurologically intact survival,

One very low quality cohort study {Roberts 2013 2107} with a total of 123 patients (downgraded for very serious
concerns about risk of bias and imprecision) showed worse outcome in patients ventilated to hypercapnia (>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
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
20
The upper limit at which PaCO2 becomes harmful is unknown, although mild hypercapnia may have some neuroprotective
effect (weak recommendation, very low quality evidence).
21

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Ilcor 2015 Sva

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Advanced airway placement (ETT vs SGA)

LMA (I) versus tracheal intubation (C)

Supraglottic airways (SGAs: Combitube and LMA) versus tracheal intubation

Airway placement (Basic vs Advanced)

Tracheal intubation (I) versus bag-mask (C)

Supraglottic airways (I) versus bag-mask (C)

ETCO2 to predict outcome of cardiac arrest

Fever after cardiac arrest

Fever after ROSC:

Fever after TTM:

Impedance threshold device

Mechanical CPR Devices

Values and Preferences Statement:

Donors with Prior CPR

Oxygen dose after ROSC in adults

Survival to discharge with favourable neurological outcome (CPC 1 or 2):

Survival to hospital discharge:

2. Hyperoxia vs. Normoxia

Survival with favourable neurological outcome (CPC 1 or 2) at 12 months:

Survival to discharge with favourable neurological outcome (CPC 1 or 2):

Survival to hospital discharge (or survival to 30 days):

Survival to ICU discharge:

3. Hypoxia vs. normoxia

Survival to hospital discharge (or survival to 30 days):

Survival to ICU discharge:

Pulmonary embolism cardiac arrest

For the important outcome of ROSC,

For the important outcome of survival to hospital discharge,

Percutaneous mechanical thrombectomy

Values and preferences statement:

Timing of drug delivery (epinephrine)

For In-Hospital Cardiac Arrests

Vasopressors for cardiac arrest (1. Epi v Placebo)

Values and Preferences Statement:

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

Values and Preferences Statement:

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

Ventilation rate during continuous chest compression

Ventilation strategy post resuscitation

For the critical outcome of neurologically intact survival,

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