advanced airway placement

Advanced airway placement (ETT vs SGA)

Question Type: Intervention

Full Question: Among adults who are in cardiac arrest in any setting (P), does tracheal tube insertion as first advanced

airway (I), compared with insertion of a supraglottic airway as first advanced airway (C), change ROSC, CPR parameters, development of aspiration pneumonia, Survival with Favorable neurological/functional

outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year (O)?

The information provided is currently in DRAFT format and is NOT a FINAL version

Consensus on Science:

EGTA (I) versus tracheal intubation (C) For the critical outcome of survival to hospital discharge we have

identified very low quality evidence (downgraded for very serious concerns about risk of bias and imprecision) from one RCT enrolling 175 OHCAs show no difference between EGTA and tracheal

intubation (OR 1.19 95% CI 0.5 - 3.0) [Goldenberg 1986 90] Combitube (I) versus tracheal intubation (C) For the critical outcome of survival to hospital discharge we have identified very low quality evidence

(downgraded for very serious concerns about risk of bias and imprecision) from one RCT enrolling 173 OHCAs that showed no difference between Combitube and tracheal intubation (OR 2.38 95% CI 0.5 –

12.1) [Rabitsch 2003 27] and very low quality evidence from one observational study of 5822 OHCAs that showed no difference between tracheal intubation by paramedics and Combitube insertion by

emergency medical technicians (EMTs) (adjusted OR 1.02; 95% CI 0.79 -1.30) [Cady 2009 495]. For the important outcome of ROSC we have identified very low quality evidence from one observational study of

5822 OHCAs that showed no difference between tracheal intubation by paramedics and Combitube insertion by emergency medical technicians (EMTs) (adjusted OR 0.93; 95% CI 0.82 -1.05). [Cady 2009

495]. LMA (I) versus tracheal intubation (C) For the critical outcome of survival to hospital discharge we have identified very low quality evidence from one observational study of 641 OHCAs that showed lower

rates of survival to hospital discharge with insertion of an LMA compared with tracheal tube (OR 0.69; 95% CI 0.4 – 1.3) [Shin 2012 313]. Supraglottic airways (SGAs: Combitube, LMA, laryngeal tube)

versus tracheal intubation For the critical outcome of favourable neurological survival we have identified low quality evidence from one observational study of 5377 OHCAs showing no difference between

tracheal intubation and insertion of a SGA (adjusted OR 0.71; 95% CI 0.39 – 1.30) [Kajino 2011 R236], from one observational study of 281,522 OHCAs showing higher rates of favourable neurological

outcome between insertion of a SGA and tracheal intubation (OR 1.11; 95% CI 1.0 – 1.2) [Hasegawa 2013 257] and from two studies showing higher rates of favourable neurological outcome between

tracheal intubation and insertion of a SGA (8701 OHCAs adjusted OR 1.44; 95% CI 1.10 – 1.88 [McMullan 2014 617]) and (10,455 OHCAs adjusted OR 1.40; 95% CI 1.04 – 1.89 [Wang 2012 1061]).

Supraglottic airways (SGAs: Combitube and LMA) versus tracheal intubation For the important outcome of ROSC we have identified very low quality evidence from one observational study of 713 OHCAs that

showed no difference between tracheal intubation and Combitube or LMA insertion by EMTs or emergency life-saving technicians (ELTs) (OR 0.65; 95% CI 0.4 – 1.2). [Yanagawa 2010 340].

Supraglottic airways (SGAs: Esophageal obturator airway and LMA) versus tracheal intubation For the

critical outcome of neurologically favourable one-month survival we have identified very low quality evidence from one observational study of 138,248 OHCAs that showed higher rates of neurologically

favourable one-month survival with tracheal intubation compared with insertion of an esophageal obturator airway or LMA (OR 0.89; 95% CI 0.8 – 1.0). [Tanabe 2013 389] For the critical outcome of

one-year survival we have identified very low quality evidence from one observational study of 923 OHCAs that showed no difference in one-year survival with tracheal intubation compared with insertion

of an esophageal obturator airway or LMA (OR 0.89; 95% CI 0.3 – 2.6). [Takei 2010 715]. For the critical outcome of one-month survival we have identified very low quality evidence from one observation

study that showed no difference in one-month survival between tracheal intubation and insertion of an esophageal obturator airway of an LMA (OR 0.75; 95% CI 0.3 – 1.9) [Takei 2010 715] and very low

quality evidence from another observation study that showed higher one-month survival with tracheal intubation compared with insertion of an esophageal obturator airway of an LMA (OR 1.03; 95% CI 0.9 –

1.1) [Tanabe 2013 389] For the important outcome of ROSC we have identified very low quality evidence from one observational study of 923 OHCAs that showed a higher rate of ROSC with tracheal intubation

compared with insertion of an esophageal obturator airway or LMA (OR 0.71; 95% CI 0.4 – 1.2). [Takei 2010 715].


Treatment Recommendation:

We suggest using either a supraglottic airway or tracheal tube as the initial advanced airway

management during CPR (weak recommendation, very low quality evidence) for out of hospital cardiac

arrest. We suggest using either a supraglottic airway or tracheal tube as the initial advanced airway

management during CPR (weak recommendation, very low quality evidence) for in hospital cardiac arrest.

CoSTR Attachments:

ALS 714 Evidence Profile for SGA versus TT_Part 2_JN_EL_21Dec14.docx

ILCOR Slides ALS 714 SGA VS TT Dallas 2015.ppt

ALS 714 Evidence Profile for SGA versus TT_Part 3_JN_EL_21Dec14.docx ALS 714 CoS and TR for SGA versus TT_JN_EL_PM_21Dec14.docx

ALS 714 Evidence Profile for SGA versus TT_Part 1_JN_EL_21Dec14.docx ALS 714 Summary of Bias Assessments for SGA versus TT5.xlsx

Airway placement (Basic vs Advanced)

Question Type:

Intervention Full Question:

Among adults who are in cardiac arrest in any setting (P), does insertion of an advanced airway (ETT or supraglottic airway) (I), compared with basic airway (bag mask +/- oropharyngeal airway) (C), change

Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days

AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC, CPR

parameters, development of aspiration pneumonia (O)?



All advanced airways (I) versus bag-mask (C) For the critical outcome of favourable neurological survival at one month we have identified very low quality evidence (downgraded for very serious concerns about

risk of bias and indirectness, and serious concerns about inconsistency) from one observational study of 648549 OHCAs showing a lower unadjusted rate of survival with insertion of an advanced airway

(tracheal tube, LMA, LT or Combitube) compared with management with a bag-mask (1.1% vs 2.9%; odds ratio [OR], 0.38; 95% CI, 0.36-0.39)) [Hasegawa 2013 257]. When adjusted for all known

variables the odds ratio was 0.32 (0.30-0.33). For the critical outcome of favourable neurological survival to hospital discharge we have identified very low quality evidence (downgraded for very serious

concerns about risk of bias and indirectness, and serious concerns about inconsistency) from one observational study of 10691 OHCAs showing a lower unadjusted rate of survival with insertion of an

advanced airway (tracheal tube, LMA, LT or Combitube) compared with management with a bag-mask (5.3% vs 18.6%; odds ratio [OR], 0.25; 95% CI, 0.2 – 0.3)) [McMullan 2014 617]. In an analysis of

3398 propensity-matched patients from the same study, the odds ratio for favourable neurological survival at hospital discharge (bag-mask versus advanced airway) adjusted for all variables was 4.19

(3.09 – 5.70). Tracheal intubation (I) versus bag-mask (C) For the critical outcome of favourable neurological survival at one month we have identified very low quality evidence (downgraded for very

serious concerns about risk of bias and indirectness, and serious concerns about inconsistency) from one observational study of 409809 OHCAs showing a lower unadjusted rate of survival with tracheal

intubation compared with management with a bag-mask (1.0% vs 2.9%; OR 0.35 (0.31-0.38)) [Hasegawa 2013 257]. In an analysis of 357228 propensity-matched patients from the same study, the

odds ratio for favourable neurological survival at one month (tracheal intubation versus bag-mask)

adjusted for all variables was 0.42 (0.34 – 0.53). For the critical outcome of favourable neurological

survival to hospital discharge we have identified very low quality evidence (downgraded for very serious concerns about risk of bias and indirectness, and serious concerns about inconsistency) from one

observational study of 7520 OHCAs showing a lower unadjusted rate of survival with tracheal intubation

compared with management with a bag-mask (5.4% vs 18.6%; odds ratio [OR], 0.25; 95% CI, 0.2 – 0.3)) [McMullan 2014 617]. Supraglottic airways (I) versus bag-mask (C) For the critical outcome of

favourable neurological survival at one month we have identified very low quality evidence (downgraded for very serious concerns about risk of bias and indirectness, and serious concerns about inconsistency)

from one observational study of 607387 OHCAs showing a lower unadjusted rate of survival with insertion of a supraglottic airway (LMA, LT or Combitube) compared with management with a bag-mask

(1.1% vs 2.9%; OR 0.38 (0.37-0.40)) [Hasegawa 2013]. In an analysis of 357228 propensity-matched patients from the same study, the odds ratio for favourable neurological survival at one month

(supraglottic airway versus bag-mask) adjusted for all variables was 0.36 (0.33-0.40).



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We suggest using either an advanced airway or a bag mask for airway management during CPR (weak recommendation, very low quality evidence) for out of hospital cardiac arrest. We suggest using either

an advanced airway or a bag mask for airway management during CPR (weak recommendation, very low quality evidence) for in hospital cardiac arrest.

CoSTR Attachments:

ALS 783 Evidence Profile SGA versus Basic_10Jan15.docx Summary of Bias Assessments for Basic versus Advanced 14Dec14.xlsx

ALS 783 CoS and TR for basic versus advanced 10Jan15.docx ALS 783 Evidence Profile Tracheal intubation versus basic_10Jan15.docx

ILCOR Slides ALS 783 Advanced versus basic Dallas 2015.ppt ALS 783 Evidence profile any advanced airway versus Basic_10Jan15.docx

Antiarrhythmic drugs for cardiac arrest

Question Type:


Among adults who are in cardiac arrest in any setting (P), does antiarrhythmic drugs (e.g. lidocaine,

amiodarone, other) administration (I), compared with not using antiarrhythmic drugs (no drug or

placebo) (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year,

ROSC (O)?



Amiodarone (I) versus no amiodarone (C) For the important outcome of ROSC, we have identified one RCT (GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of (or developing) VF

or pulseless VT refractory to 3 shocks showing an improved rate of ROSC with administration of amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (64% vs 41%; p=0.03)

[Kundenchuk 1999]. For the critical outcome of survival at discharge, we have identified one RCT (GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of (or developing) VF or

pulseless VT refractory to 3 shocks showing a similar rate of survival with administration of amiodarone (300 mg after 1 mg of adrenaline) compared with no drug (13.4% vs 13.2%; p=ns) [Kundenchuk 1999].

For the critical outcome of survival with favorable neurological/functional outcome at discharge, we have identified one RCT (GRADE: high) of 504 patients who suffered from OHCA with an initial rhythm of (or

developing) VF or pulseless VT refractory to 3 shocks showing a similar rate of survival with favorable neurological outcome with administration of amiodarone (300 mg after 1 mg of adrenaline) compared

with no drug (53% vs 50% of survivors; p=ns) [Kundenchuk 1999]. Lidocaine (I) versus no lidocaine (C) For the important outcome of ROSC, we identified 2 retrospective observational single center studies

(GRADE: very low; very serious risk of bias) with conflicting results: - Herlitz [1997] et al. showed in 290 patients who suffered from OHCA with VF refractory to 3 shocks an improved rate of ROSC with

administration of lidocaine (50 mg, repeatable up to 200 mg) compared with no drug (45% vs 23%; p



There are no studies that show improved survival to hospital discharge or functional survival with the use of antiarrhythmics in cardiac arrest patients refractory to VF/pVT. - We suggest the use of amiodarone in

adult patients who suffer OHCA with refractory VF/pVT to improve rates of ROSC (Weak recommendation; high confidence in effect estimate). - Clinicians might consider lidocaine or nifekalant

for in adult patients who suffer OHCA and IHCA , respectively (Weak recommendation, very low

confidence in effect estimates). - We suggest against the use of magnesium in adult patients who are in OHCA in any rhythm (Strong recommendation, moderate confidence in effect estimate).

CoSTR Attachments:

ALS 428 should-lidocaine-vs-no-lidocaine-be-used-for-adults-who-are-in-cardiac-arrest-in-any-

setting.pdf ALS 428 should-nifekalant-vs-no-nifekalant-be-used-for-adults-who-are-in-cardiac-arrest-in-any-

setting.pdf ALS 428 should-magnesium-vs-no-magnesium-be-used-for-adults-who-are-in-cardiac-arrest-in-any-

setting.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/21/ALS%20783%20Evidence%20Profile%20SGA%20versus%20Basic_10Jan15.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/21/Summary%20of%20Bias%20Assessments%20for%20Basic%20versus%20Advanced%2014Dec14.xlsx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/21/ALS%20783%20CoS%20and%20TR%20for%20basic%20versus%20advanced%2010Jan15.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/21/ALS%20783%20Evidence%20Profile%20Tracheal%20intubation%20versus%20basic_10Jan15.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/21/ILCOR%20Slides%20ALS%20783%20Advanced%20versus%20basic%20Dallas%202015.ppt

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/21/ALS%20783%20Evidence%20profile%20any%20advanced%20airway%20versus%20Basic_10Jan15.docx

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

Antiarrhythmic drugs post resuscitation

Question Type:


Among adults who are experiencing ROSC after cardiac arrest in any setting (P), does prophylactic antiarrhythmic drugs given immediately after ROSC (I), compared with no use of antiarrhythmic drugs

(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, development of cardiac arrest, Survival only at discharge, 30 days, 60 days, 180

days AND/OR 1 year, recurrence of VF, incidence of arrhythmias (O)?



Proposed Consensus on Science statements B-blockers (I) versus no b-blockers (C) For the critical outcome of survival at 6 months we have identified low quality evidence from one observational study of

98 patients resuscitated from OHCA showing a higher unadjusted rate of survival with administration of b-blockers (metoprolol or bisoprolol) for 72 hours post-ROSC compared with no drug (65.8% vs 21.1%;

p< 0.0001). In an unadjusted analysis on 1721 patients the rate of recurrence of VF was also lower (16.7% vs 37.4%, p< 0.0001), as it was in an adjusted analysis (OR 1.49, 1.15–1.95 95% CI)

[Kudenchuk 2013]. 1692 papers have been considered from which 39 from fulfilled the search. After reviewing them, there is no convincing evidence that the routine use of magnesium, amiodarone,

lidocaine, procainamide, bretylium and nifekalant after ROSC in human CPR increased survival to

hospital discharge. Antiarrhythmic drugs may improve immediate recovery from cardiac arrest (especially those related to ventricular tachyarrhythmias) but fail to assure survival thereafter. Lidocaine,

procainamide and bretylium have been extensively reviewed in previous issues of CoSTR (1005-2010) showing no important effects and will not be considered in this report. From all the remaining

antiarrhythmic drugs, the one with best results seem to be amiodarone. Newer drugs, like nifekalant, have not been extensively tested in humans although some observations, non-randomized trials and

animal studies show promising results when compared with amiodarone. Thus the last mentioned drug is still the best available one to be considered for arrhythmias involved in cardiac arrest in the early stages

(arrival to the hospital from OHCA) although no changes have been registered in survival after hospital discharge.



We are making no recommendation with regards to the routine prophylactic use of antiarrhythmic drugs

post-ROSC in all OHCA patients (GRADE used for evidence evaluation and synthesis only - very low confidence in effect estimate). Clinicians might consider either lidocaine or b-blockers in post-ROSC

patients who had VT/VF as their initial rhythm (Weak recommendation, very low confidence in effect estimate).

CoSTR Attachments:

ALS493 Antiarrhythmics Post ROSC 20150110_.pptx

CoSTR Statement - ALS 493 Antiarrhythmic drugs post resuscitation 20150110.docx Pellis - Grade Table.docx

Cardiac arrest during PCI


Full Question: Among adults who have a cardiac arrest in the cardiac cathether laboratory (P), does any special

intervention or change in care (e.g. catheterization during CPR, cardiopulmonary bypass, balloon pump, different timing of shocks) (I), compared with standard resuscitation care (e.g. CPR, drugs and shocks

according to 2010 treatment algorithm) (C), change Survival with Favorable neurological/functional

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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)?



There were no comparative studies evaluating the survival benefit of mechanical CPR, Individual

noncomparative case series reported variable survival rates. For the outcomes of “survival with favourable neurological/functional outcome at discharge, 30 days, 60 days, 90 days, 180 days, and 1

year” we identified no papers. For the outcomes of “survival at 30 days, 60 days, 90 days, and 180 days” we identified no papers. For the outcomes of ROSC, ‘survival at discharge’ and ‘1-year survival’ we

identified 1 very low quality evidence (downgraded for risk of bias and imprecision) observational study that compared ECMO vs. IABP in a total of 21 patients. The study showed improved rates of ROSC 9 of

13 (69.23%) vs. 1 of 8 (12.5%), improved survival to discharge 8 of 13 (61.5%) compared with 0 of 8 (0%), and increased 1-year survival 7 of 13 (53.85%) compared to 0 of 8 (0%) for ECMO compared to

IABP in patients who have a cardiac arrest in the cardiac catheterization laboratory. Individual non-comparative case series of ECMO also observed a high rate of survival.



We suggest using ECLS (cardiopulmonary bypass) as a rescue treatment when initial therapy is failing

for cardiac arrest that occurs during percutaneous coronary interventions (weak recommendation, very low quality evidence). We are making no recommendations with regard to the routine use of mechanical

CPR in this setting (GRADE has no data).

CoSTR Attachments:

PCI_CA - Dallas 2015.pptx 2015 ALS PCI CoSTR StatementDraft.docx

Bias and Data copy5.xlsx

eCPR vs manual CPR

Question Type:


Among adults who are in cardiac arrest in any setting (P), does the use of extracorporeal CPR techniques (eCPR)(including ECMO or cardiopulmonary bypass)

(I), compared with manual CPR or mechanical CPR (C), change survival to 180 days with good neurological outcome, survival with favorable neurologic

outcome, survival to hospital discharge with good neurological outcome, survival to hospital discharge, ROSC (O)?



For the critical outcome of “neurological outcome at 90 days” after OHCA we have identified very low

quality evidence from one non-RCT enrolling 39 patients showing no benefit (OR 0.22 95% CI 0.04-

1.20). For the critical outcome of “neurological outcome at 180 days” after OHCA we have identified low

quality evidence from one non-RCT enrolling 359 patients showing benefit (OR 0.22 95% CI 0.09-0.61). For the critical outcome of “neurological outcome at hospital discharge” after IHCA we have identified

very low quality evidence from 3 non-RCTs enrolling 410 patients showing benefit (OR 0.42 95% CI 0.24-0.72). For the critical outcome of “neurological outcome at one year” after IHCA we have identified

low quality evidence from 2 non-RCTs enrolling 199 patients showing no benefit (OR 0.54 95% CI 0.24-1.23).



We suggest using eCPR for OHCA (weak recommendation, low quality of evidence). We suggest using

eCPR for IHCA (weak recommendation, low quality of evidence). _______________________________________________________________________________ We

suggest using eCPR for select* populations of OHCA (weak recommendation, low quality of evidence). We suggest using eCPR for select* populations of IHCA (weak recommendation, low quality of evidence).

*In making these recommendations we note that the published series used rigorous inclusion criteria to

select patients for eCPR, and that our recommendation should apply to similar populations.

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CoSTR Attachments:

eCPRvsManualCPR_Summary.docx

eCPR_ILCORSlideDec2014.pptx eCPRvsManualCPR_SOF.docx

ETCO2 to predict outcome of cardiac arrest

Question Type:

Prognostic Full Question:

Among adults who are in cardiac arrest in any setting (P), does any end-tidal CO2 level value, when present (I), compared with any end-tidal CO2 level below that value (C), change (O)?



For the important outcome of “ROSC” we have identified low quality evidence from 3 observational

studies enrolling 302 patients (Ahrens 2001, 391; Callaham 1990, 358; Cantineau 1996, 791) showing a correlation with Initial ETCO2≥ 10 mmHg when compared to < 10 mmHg (OR 10.7 95% CI 5.6 – 20.3).

For the important outcome of “ROSC” we have identified low quality evidence from 3 observational studies enrolling 367 patients (Ahrens 2001, 391; Levine 1997, 301; Wayne 1995, 762) showing

correlation with 20 min ETCO2≥ 10 mmHg when compared to < 10 mmHg (OR 181.6 95% CI 40.1 – 822.6). For the critical outcome of “survival at discharge” we have identified low quality evidence from 1

observational study enrolling 127 patients (Ahrens 2001, 391) showing a correlation with Initial ETCO2≥ 10 mmHg when compared to < 10 mmHg (OR 11.4 95% CI 1.4 – 90.2). For the critical outcome of

“survival at discharge” we have identified low quality evidence from 1 observational study enrolling 127

patients (Ahrens 2001, 391) showing a correlation with 20 min ETCO2≥ 20 mmHg when compared to < 20 mmHg (OR 20.0 95% CI 2.0 – 203.3). We did not identify any evidence to address the critical

outcome of “neurologically intact survival”.



We suggest that ETCO2≥ 10 mmHg, measured after the intubation or at 20 min of resuscitation, may be a predictor of ROSC (weak recommendation, low quality of evidence). We suggest that ETCO2≥ 10

mmHg, measured after the intubation, or ETCO2≥ 20 mmHg, measured at 20 min of resuscitation, may be a predictor of survival at discharge (weak recommendation, low quality of evidence). Although certain

ETCO2 cutoff values appear to be a strong predictor of ROSC and mortality, their utility in accurately predict outcome during CPR is not established. Thus, we recommend against using ETCO2 cutoff values

alone as a mortality predictor or on the decision to stop the resuscitation attempt (weak recommendation, low quality of evidence).

CoSTR Attachments:

CoS and TR ETCO2.docx

ILCOR Dallas 2015 ETCO2.pptx

SOF Table ETCO2.docx

Exhaled CO2 detection and esophageal detection devices


Full Question: Among adults who are in cardiac arrest, needing/with an advanced airway, in any setting (P), does use

of devices (e.g. 1. Waveform Capnography, 2. CO2 Detection Device, 3. Esophageal detector device, or 4. Tracheal ultrasound) (I), compared with not using devices (C), change placement of the ET tube

between the vocal cords and the carina, success of intubation (O)?



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https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/146/eCPR_ILCORSlideDec2014.pptx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/146/eCPRvsManualCPR_SOF.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/22/CoS%20and%20TR%20ETCO2.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/22/ILCOR%20Dallas%202015%20ETCO2.pptx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/22/SOF%20Table%20ETCO2.docx

For the critical outcome of confirming placement of the endotracheal tube between the cords and the carina we have identified low grade evidence to support the use of waveform capnography.



Our treatment recommendations are unchanged from 2010 guidance. Waveform capnography is

recommended to confirm and continuously monitor the position of a tracheal tube in victims of cardiac arrest. It should be used in addition to clinical assessment - auscultation and direct visualization are

suggested (strong recommendation based on very low quality evidence). If waveform capnography is not available, the use of a non-waveform carbon dioxide detector or esophageal detector device in addition

to clinical assessment (auscultation and direct visualization are suggested) is an alternative.

CoSTR Attachments:

ALS ETT PICO 469.docx

Fever after cardiac arrest

Question Type:


Adults with ROSC after cardiac arrest in any setting (P), does Prevention of fever to maintain strict normothermia (I), compared with No fever control (C), change Survival with Favorable

neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year (O)?



No interventional or observational studies were identified addressing whether fever prevention (or

treatment) after cardiac arrest improves outcome. Fever after ROSC: For the critical outcomes of survival with good neurologic/functional outcome and/or survival only, we found very low quality

evidence from 5 observational studies (downgraded for risk of bias and indirectness) that fever after ROSC is associated with poor outcome when TTM is not used [Zeiner 2001 2007, Langhelle 2003 247,

Nolan 2007 1207, Suffoletto 2009 1365, Gebhardt 2013 1062]. Fever after TTM: For the critical outcomes of survival with good neurologic/functional outcome and/or survival only, we found very low

quality evidence from 6 observational studies (n =856) (downgraded for risk of bias and indirectness) that fever after TTM is not associated with outcome [Aldhoon 2012 E68, Benz-Woerner 2012 338,

Bouwes 2012 996, Gebhardt 2013 1062, Leary 2013 1056, Cocchi 2014 365] For the same critical outcomes we also found very low quality evidence from 2 observational studies (n = 411) (downgraded

for risk of bias, inconsistency and indirectness) that fever after TTM is associated with poor outcome [Bro-Jeppesen 2013 1734, Winters 2013 1245]



We suggest prevention and treatment of fever in persistently comatose adults after completion of

targeted temperature management between 32 and 36 degrees Celsius (weak recommendation, very low quality evidence)

CoSTR Attachments:

ALS 879. Fever after CA PICO. Rapid fire presentation. Dallas 2015.pptx ALS 879. Fever after CA PICO. Full Presentation. Dallas 2015.pptx

Glucose control following resuscitation

Question Type:


Among adults with ROSC after cardiac arrest in any setting (P), does a specific target range for blood glucose management (eg. strict 4-6 mmol/L) (I), compared with any other target range (C), change

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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)?



For the critical outcome of survival to hospital discharge, one RCT of 90 subjects, downgraded for risk of

bias, found no reduction in 30-day mortality (RR 0.94; 95%CI 0.53-1.68) when subjects were assigned to strict (4-6mmol/L) versus moderate (6-8 mmol/L) glucose control (Oksanen 2007). For the critical

outcome of survival to hospital discharge, one before-and-after observational study of 119 subjects found reduced in-hospital mortality (RR 0.46; 95%CI 0.28-0.76) after implementation of a bundle of

care that included defined glucose management (5-8 mmil/L), but the isolated effect of glucose management is confounded by and cannot be separated from the effect of other parts of the bundle

(Sunde 2007).



We suggest not selecting any specific target range of glucose management versus any other target range in adults with ROSC after cardiac arrest (weak recommendation, moderate quality of evidence). In

making this recommendation, we noted that strict glycemic control is labor intensive. In other populations, implementation of strict glycemic control is associated with increased episode of

hypoglycemia, which might be detrimental. There are no data that the approach to glucose management chosen for other critical care populations should be modified for the cardiac arrest population.

CoSTR Attachments:

SummarofBiasAssessmentsGlucose.xlsx

GlucosePICO_draft2.docx ILCOR Data Collection Form Glucose jz.xls

GlucosePICO_slides.ppt SOFtable.tiff

GRADEtable.tiff

Hemodynamic support post resuscitation

Question Type:


Among adults with ROSC after cardiac arrest in any setting (P), does titration of therapy to achieve a specific hemodynamic goal goal (e.g. mean arterial pressure > 65 mmHg) (I), compared with no

hemodynamic goal (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR

1 year (O)?



There are no RCTs addressing hemodynamic goals post resuscitation. 1. Titration of therapy to achieve a

specific hemodynamic goal (e.g. mean arterial pressure > 65 mmHg) compared to no hemodynamic goal

For the critical outcome of survival with favorable neurological/functional outcome we have identified very low quality evidence (downgraded for risks of bias and publication bias) from one multicentre

retrospective non-intervention study including 8736 subjects that found post return of spontaneous circulation (ROSC) systolic blood pressure (SBP) 80 mm Hg showed no difference in mortality or

neurological outcome at hospital discharge (Gaieski 2009, 418). One prospective observational study of 118 patients using historical controls and a aiming for MAP >65 mm Hg showed survival to hospital

discharge with a favourable neurological outcome in 34/61 (56%) up to one year, versus 15/58 (26%) in the control period (OR 3.61, CI 1.66-7.84, p=0.001) (Sunde 2007, 29). One cohort study of 148 patients

when a MAP 100 mm Hg or < 100 mm Hg after ROSC. Good neurological recovery was independently and directly related to MAP measured during 2 hours after ROSC (rs=.26; P 65 mmHg within 6 hours,

resulted in an in-hospital mortality of 55.2% (bundle) vs. 69.2% (prebundle) (P = 0.29). Bundle patients achieved good neurologic outcome compared patients, CPC 1 or 2 in 31 vs. 12% patients, respectively (P

= 0.08) (Walters 2011, 360). One prospective single centre observational study assessed the association between increasing time-weighted average mean arterial pressures and good neurologic outcome.

Among 151 patients receiving a bundle of therapies, 44 (29%) experienced good neurologic outcome and a time-weighted average MAP threshold > 70 mm Hg had the strongest association with good

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/144/SummarofBiasAssessmentsGlucose.xlsx

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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).



We suggest hemodynamic goals (e.g. MAP, SBP) are considered during post resuscitation care and as

part of any bundle of post-resuscitation interventions. (weak recommendation, low quality evidence). There is insufficient evidence to recommend specific hemodynamic goals, such goals should be

considered on an individual patient basis and are likely to be influenced by post resuscitation status and pre-existing morbidities that are considered during post resuscitation care. (weak recommendation, low

quality evidence).

CoSTR Attachments:

should-a-bundle-of-goal-directed-therapies-including-achieving-bp-goal-vs-no-bundlenot-achieving-

b2.doc should-a-blood-pressure-target-achieved-vs-blood-pressure-target-not-achieved-be-used-for-adults-

wi.doc ALS570_HaemodynamicsupportafterROSC_MP_15Jan2015corrected3.2.15.ppt

Impedance threshold device

Question Type:


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-

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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 demonstrate a clinically significant benefit from the addition of the ITD to ACD CPR (when

compared with standard CPR): RR 1.39 (95% CI 1.04 to 1.85, or from 2 more to 47 more per 1000). For the critical outcome of survival to hospital discharge, there were two RCTs (Wolcke 2003, 2201 and

Frascone 2013, 1214 (which incorporated data published in Aufderheide 2011, 301)) of very low quality (downgraded for risk of bias, indirectness and suspected publication bias) in a total of 2948 out-of-

hospital cardiac arrests that were unable to demonstrate a clinically significant benefit from the addition of the ITD to ACD CPR (when compared with standard CPR): RR 1.17 (95% CI 0.94 to 1.45)(Frascone

2013) and RR 1.41 (95% CI 0.75 to 2.66)(Wolcke 2003, 2201).



Impedance Threshold Device + Standard CPR (I) vs Standard CPR (C): We recommned against routine use of ITD in addition to standard CPR (strong recommendation, high quality of evidence). Values and

preferences statement: In making this recommendation we place a higher value on not allocating resources to an ineffective intervention over any yet to be proven benefit for critical or important

outcomes. Impedance Threshold Device + Active Compression Decompression CPR (I) vs Active Compression Decompression CPR (C): We suggest against the routine use of ITD in addition to Active

Compression-Decompression CPR (weak recommendation, very low quality of evidence). Values and 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 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.

CoSTR Attachments:

ITDACDvsStandard2May2014.pdf ITDACDvsACDEP1May2014.pdf

ITDnoITD2May2014.pdf

Induced Hypothermia

Question Type:

Intervention

Full Question:

Among patients with ROSC after cardiac arrest in any setting (P), does inducing mild hypothermia (target temperature 32-34ºC) (I), compared with normothermia (36-37ºC) (C), change Survival with Favorable




Targeted temperature management (I) vs no targeted temperature management (C): Out-of-hospital

cardiac arrest with shockable rhythm: For the critical outcome of “survival with good neurological outcome,” we have identified low quality evidence from one randomized control trial (RCT) [The

Hypothermia After Cardiac Arrest Study Group,2002;549] and one pseudorandomized trial [Bernard;2002; 557] enrolling 275 and 77 patients, demonstrating a benefit in patients with out of

hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as an initial rhythm. In these studies, cooling to 32-34 degrees Celsius compared to no temperature

management was associated with a risk ratio (RR) and odds ratio (OR) for good neurologic outcome at 6 months and hospital discharge of 1.4 (95% CI 1.08-1.81) and 2.65 (95% CI 1.02-6.88), respectively.

For the critical outcome of “survival,” low quality evidence in the larger study demonstrates benefit in

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patients treated with induced hypothermia (RR for 180-day mortality 0.74, 95% CI 0.58-0.95) [The Hypothermia After Cardiac Arrest Study Group,2002;549] while the other study found no significant

difference (51% vs 68% hospital mortality, p=0.145).[Bernard;2002; 557] Out-of-hospital cardiac arrest with nonshockable rhythm: We found no randomized controlled trials comparing mild induced

hypothermia (32-34 degrees Celsius) to no temperature management in patients with OHCA with

pulseless electrical activity or asystole (i.e. nonshockable) as the initial rhythm.For the critical outcome

of “survival with good neurologic outcome”, we found three cohort studies including a total of 1,034 patients, providing overall very low-quality evidence for no difference in poor neurologic outcome in

patients with nonshockable OHCA (adjusted pooled OR, 0.90 [95% CI, 0.45 – 1.82].[Dumas; 2011; 877, Testori;2011;1162, Vaahersalo;826; 2013] One additional retrospective study utilizing a large registry,

including 1830 patients, provided very low quality evidence for an increase in poor neurologic outcome in patients with nonshockable OHCA.[Mader;2014;21] This data was not pooled with the above studies and

an adjusted OR was not included in the CoSTR due to the lack of temperature data, limited patient information, and inconsistent results within the study. For the critical outcome of “survival,” we found

very low quality evidence of a benefit in mortality at 6 months (OR 0.56, 95% CI 0.34-0.93) from one of these studes.[Testori;2011;1162] In-hospital cardiac arrest: We found no 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).[Nichol;2013;620] For the critical outcome of “neurologically favorable survival”, we found very low quality evidence from the same observational

study showing no benefit (OR 0.93, 95% CI 0.65-1.32). This evidence was downgraded for high probability of selection bias, residual confounding, and a low prevalence of patients (2.6%) receiving the

intervention. Note: Although we found numerous observational studies on the implementation of temperature management, these data are extremely difficult to interpret in light of other changes in

post-cardiac arrest care that accompanied implementation, making it impossible to isolate the effect of

temperature on outcomes after cardiac arrest. For this reason, we excluded all before and after studies. Other observational studies with concurrent controls also represent low quality evidence due to residual

confounding and other factors. We therefore did not include these in the consensus on science, except for specific patient populations lacking higher quality (i.e. RCT) evidence. Is there evidence for an ideal

temperature (I) when using targeted temperature management? For the critical outcomes of “survival” and “survival with good neurologic outcome,” we found moderate quality evidence from one RCT

including 939 patients. This study compared cooling to 33 degrees Celsius compared to tight temperature control at 36 degrees Celsius in adult patients with OHCA of any initial rhythm except

unwitnessed asystole, and found no benefit (HR for mortality at end of trial 1.06, 95% CI 0.89-1.28; RR for death or poor neurologic outcome at 6 months 1.02, 95% CI 0.88-1.16).[Nielsen;2013;2197] For the

critical outcome of “survival with good neurologic outcome” we found low quality evidence in one additional small pilot RCT enrolling 36 patients comparing 32 vs 34 degrees Celsius in patients with

OHCA VT/VF or asystole.[Lopez-de-sa;2012;2826] This study found no benefit (neurologically intact survival 44.4% vs 11.1%, p=0.12), although with only 36 patients it was underpowered.



We recommend targeted temperature management as opposed to no targeted temperature management

for adults with OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong recommendation, low-quality evidence). We suggest targeted temperature management as opposed to

no targeted temperature management for adults with OHCA with an initial nonshockable rhythm (weak recommendation, very low-quality evidence) who remain unresponsive after ROSC. We suggest targeted

temperature management as opposed to no targeted temperature management for adults with IHCA (weak recommendation, very low-quality evidence) with any initial rhythm who remain unresponsive

after ROSC. We recommend selecting and maintaining a constant, target temperature between 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.

CoSTR Attachments:

ALS 790. TTM Main. Full presentation. Dallas 2015.pptx ALS 790. GRADE Tables - TTM main question.pdf

Induced Hypothermia (duration)

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Full Question: In patients with ROSC after cardiac arrest in any setting (P), does induction and maintenance of

hypothermia for any duration other than 24 hours (I), compared with induction and maintenance of

hypothermia for a duration of 24 hours (C), change Survival with Favorable neurological/functional

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)?



We found no human interventional studies comparing different durations of targeted temperature

management after cardiac arrest with ROSC. One observational trial provided overall very low-quality evidence for no difference in duration of hypothermia in those with a good versus a poor neurologic

outcome [Yokoyama 2011 1063]. One observation trial provided overall very low-quality evidence for no difference in mortality or poor neurological outcome with 24 hours compared to 72 hours of hypothermia

[Lee 2014 297]. Previous trials for targeted temperature management ranged from 12 to 28 hours depending on the trial [Bernard 2002 557, HACA 2002 549, Nielsen 2013 2197]. One trial provided strict

normothermia (< 37.5 oC) after rewarming until 72 hours after ROSC [Nielsen 2013 2197]. However this intervention was applied to both groups and therefore treatment effect cannot be assessed.



We suggest that if targeted temperature management is used, duration should be at least 24 hours as

done in the two largest previous RCTs [HACA 2002 549, Nielsen 2013 2197] (weak recommendation, very low-quality evidence).

CoSTR Attachments:

ALS 791. TTM Duration. Rapid fire presentation. Dallas 2015.pptx

ALS 791. TTM Duration. Full presentation. Dallas 2015.pptx

Induced Hypothermia (timing)

Question Type:


Among patients with return of pulses after cardiac arrest in any setting (P), does induction of hypothermia before some time point (e.g. 1 hour after ROSC or prior to hospital arrival) (I), compared

with induction of hypothermia after that time point (C), change Survival with Favorable 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)?



Seven RCTs were identified for inclusion from 2286 studies generated from the search. Five [Kim 2007

3064, Kamarainen 2009 900, Bernard 2010 737, Bernard 2012 747, Kim 2014 45] of the 7 studies used

cold intravenous fluids after ROSC to induce hypothermia, one study used cold intravenous fluid during resuscitation [Debaty 2014 1832] and one study used intra-arrest intranasal cooling [Castren 2012

729].The volume of cold fluid ranged from 20 – 30 ml/kg and up to 2 liters though some patients did not receive the full amount prior to hospital arrival. One small feasibility trial was not included [Callaway

2002 159]. All 7 included studies suffered from the unavoidable lack of blinding of the clinical team, and 3 also failed to blind the outcomes assessors. Five of the studies, enrolling a total of 1,867 patients with

OHCA, evaluated the outcome of poor neurologic outcome [Kamarainen 2009 900, Castren 2012 729, Bernard 2010 737, Bernard 2012 747, Kim 2014 45]. Meta-analysis of these studies showed that

initiation of induced hypothermia in the prehospital environment did not differ from no initiation of prehospital induced hypothermia for poor neurologic outcome (RR, 1.00; 95% CI, 0.95–1.06). All 7 trials

examined the outcome of mortality, and meta-analysis of the total of 2,237 patients provided moderate-quality evidence demonstrating no overall difference in mortality for patients treated with prehospital

cooling (RR, 0.98; 95% CI, 0.92–1.04) compared to those who did not receive prehospital cooling. When reviewed individually, none of the trials found an effect on either poor neurologic outcome or mortality.

Meta-analysis of 4 RCTs that examined the outcome of re-arrest demonstrated an increased risk for re-arrest among patients who received prehospital induced hypothermia (RR, 1.22; 95% CI, 1.01–1.46)

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[Kim 2007 3064, Kamarainen 2009 900, Bernard 2012 747, Kim 2014 45]. This result was driven by data from the largest trial [Kim 2014 45]. Six trials included pulmonary edema as an outcome. Three of

these recorded no pulmonary edema in either group. The remaining three did record patients who had pulmonary edema. Two small pilot trials [Kim 2007 3064, Depaty 2014 1832] found no statistically

significant difference between the groups whereas the larger trial by Kim et al. found an increase in

pulmonary edema in patients who received prehospital cooling (RR, 1.34; 95% CI, 1.15-1.57) [ Kim

2014 45].



We recommend against routine use of prehospital cooling with rapid infusion of large volumes of cold intravenous fluid immediately after ROSC (strong recommendation, moderate-quality evidence).

CoSTR Attachments:

ALS 802. GRADE Tables - TTM timing question.pdf ALS 802. TTM Timing. Full presentation. Dallas 2015.pptx

Lipid Therapy for Cardiac Arrest

Question Type:


In adult patients with cardiac arrest due to suspected drug toxicity (e.g. local anesthetics, tricyclic antidepressants, or others) (P), does administration of intravenous lipid (I), compared with no

intravenous lipid (C), change Survival with Favorable neurological/functional outcome at discharge, 30 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 outcomes of neurologically intact survival and survival and for the important outcome of ROSC, we have not identified any studies of sufficient quality or relevance to the PICO question to

include in this review.



Due to a lack of human comparative studies in cardiac arrest and peri-arrest states, we are unable to make any evidence-based treatment recommendation about the use of intravenous lipid emulsion to

treat toxin-induced cardiac arrest.

CoSTR Attachments:

ALS-834 Lipid Therapy for Cardiac Arrest 2015-02-03 posted for public comment.pdf

Mechanical CPR Devices

Question Type:


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

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chest compression device compared to manual chest compressions (7.5% of patients in the control group versus 3.1% in the intervention group, p=0.006). Two other RCTs (Wik 2014 741, Rubertsson

2013 53) (n=6820), one using a load-distributing band and the other a LUCAS (Lund University Cardiac Arrest System), did not demonstrate benefit or harm when compared with manual chest compressions.

For the critical outcomes of survival at 30 days with good neurologic outcome and survival at 180 days

with good neurologic outcome, we identified moderate quality evidence from 1 RCT (Rubertsson 2013

53) using a LUCAS device and enrolling 2589 OHCA patients that did not demonstrate benefit or harm when compared with manual chest compressions. For the critical outcome of survival to hospital

discharge, we identified moderate quality evidence from 5 RCTs (Hallstrom 2006 2620, Lu 2010 496, Rubertsson 2013 53, Smekal 2011 702, Wik 2014 741) enrolling 7734 OHCA patients and 150 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) . Three studies

(Dickinson 1998 289, Halperin 1993 762, Lu 2010 496) (n=201) demonstrated benefit with mechanical chest compression devices. One study (Wik 2014 741)(n=4231) demonstrated harm with mechanical

devices however there was no adjustment for interim analyses. Three studies (Perkins 2014 1, Rubertsson 2013 53, Smekal 2011 702)(n=7206) did not demonstrate benefit or harm when compared

to manual chest compressions.



We suggest mechanical chest compression devices should not be considered the standard of care for cardiac arrest patients, but can be considered a reasonable alternative to high quality manual chest

compressions in some settings (weak recommendation, moderate quality of evidence). Values and Preferences Statement: In making this recommendation we place value on data from a large, high-

quality RCT demonstrating equivalence between high quality manual chest compressions and mechanical chest compressions. Local considerations such as relative costs and resource availability for maintenance

of high quality manual chest compressions and mechanical chest compression device implementation should guide decisions around which mode of chest compression delivery is most appropriate. Also, there

may be scenarios not directly addressed in the literature reviewed to support this treatment recommendation such as CPR in a moving ambulance, in the angiography suite or during preparation for

ECLS, where mechanical chest compressions are more practical.

CoSTR Attachments:

MEch CPR ev profile table Jan 22 2015.docx

Opioid toxicity

Question Type:


Among adults who are in cardiac arrest or respiratory arrest due to opioid toxicity in any setting (P), does any adjunct therapy (e.g. naloxone, bicarbonate, or other drugs) (I), compared with usual ALS with

no adjunct therapy (C), change Survival with Favorable neurological/functional outcome at discharge, 30 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)?


https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/29/MEch%20CPR%20ev%20profile%20table%20Jan%2022%202015.docx


• For the important outcome of Survival with Favorable neurological/functional outcome at discharge, 30

days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC, following opioid induced cardiac arrest, we found 0 publications providing no data

upon which to make a recommendation beyond standard ALS care • For the important outcome of

Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC, following

opioid induced respiratory arrest, • 12 publications were included • 5 assessed the route of naloxone administration, • 7 assessed the safety of naloxone use or were observational studies of naloxone use.



• We recommend the use of naloxone by intravenous, intramuscular, subcutaneous, intraosseous, or

intranasal routes in respiratory arrest presumed due to opioid toxicity. (strong recommendation, very low quality of evidence). Dosage of naloxone varies by route. • We can make no recommendation

regarding the modification of standard ALS in opioid induced cardiac arrest.

CoSTR Attachments:

C2015 Rapid Fire ILCOR OPIATE ALS Slide Template.1.7.15.potx

Organ donation

Question Type:


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

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outcome when organs were recovered from non-heart beating donors with ongoing CPR compared to other types of donors for adult kidneys (177 organs, 2 studies) or adult livers (34 organs, 1 study).



Treatment Recommendation: 1. We recommend that all patients who have restoration of circulation after

CPR and who subsequently progress to death be evaluated for organ donation (strong recommendation, low quality of evidence). In making this recommendation, we consider the absence of any evidence of

worse graft function from donors with antecedent CPR, the desirability of providing more organs to waiting recipients, and the absence of any risk to the donor. As in all organ donation, the function of the

donated organ determines whether procurement and transplantation proceed. Therefore, there is also precaution to ensure the safety of the recipient. 2. We suggest that patients who fail to have restoration

of circulation after CPR and who would otherwise have termination of efforts be considered candidates for kidney or liver donation in settings where programs exist (weak recommendation, low quality of

evidence). In making this recommendation, we consider the evidence that kidney grafts obtained from donors with ongoing CPR can function at rates comparable to kidneys obtained from other donors, and

that recipients can safely tolerate delayed graft function that is common with kidneys obtained in this manner. We also consider the immediate life-saving potential of liver grafts, which offsets the potentially

greater rate of long-term graft failure in livers obtained from donors with ongoing CPR.

CoSTR Attachments:

SummarofBiasAssessmentsOrganDonationFinal.xlsx

AgreementDisagreement_Updated_Reasons_final.xlsx TableResultsFinal.docx

ILCORDataCollectionFormOrganDonationFinal.xls

Oxygen dose after ROSC in adults


Full Question: Among adults who have ROSC after cardiac arrest in any setting (P), does an inspired oxygen

concentration titrated to oxygenation (normal oxygen saturation or partial pressure of oxygen) (I), compared with the use of 100% inspired oxygen concentration (C), change survival to 30 days with

good neurological outcome, survival to hospital discharge with good neurological outcome, improve survival, survival to 30 days, survival to hospital discharge (O)?



1. 30% inspired oxygen for 60 minutes after ROSC vs. 100% inspired oxygen for 60 minutes after ROSC

Survival to discharge with favourable neurological outcome (CPC 1 or 2): [1 study, observational, Kuisma 2006 199]. For the critical outcome of survival to hospital discharge with favourable neurological

outcome (CPC 1 or 2) we have identified very low quality evidence (downgraded for risk of bias, imprecision, lack of blinding, indirectness) from one RCT [Kuisma 2006 199] enrolling 32 OHCA (of which

4 excluded) patients that showed no difference between 30% inspired oxygen for 60 minutes after ROSC vs.100% inspired oxygen for 60 minutes after ROSC (8/14 vs. 6/14, unadjusted RR for survival1.33

[95% CI 0.63 to 2.84] p=0.46) . Survival to hospital discharge: [1 study, observational, Kuisma 2006 199]. For the critical outcome of survival to hospital discharge we have identified very low quality

evidence (downgraded for small numbers, lack of blinding, indirectness, misallocation of patients) from one RCT [Kuisma 2006 199] enrolling 32 OHCA (of which 4 excluded) patients that showed no difference

between 30% inspired oxygen for 60 minutes after ROSC and 100% inspired oxygen for 60 minutes of

after ROSC (10/14 vs. 10/14, unadjusted RR for survival 1.0 [95% CI 0.63 to 1.60] p=1.00). 2. Hyperoxia vs. Normoxia Survival with favourable neurological outcome (CPC 1 or 2) at 12 months: [1

study , observational, Vaahersalo 2014 1463] For the critical outcome of survival with favourable neurological outcome (CPC 1 or 2) at 12 months we have identified very low quality evidence from 1

study [Vaahersalo 2014 1463] (downgraded for very serious risk of bias, and indirectness) that showed no harmful effect from hyperoxia during the first 24 hours of ICU care. Survival to discharge with

favourable neurological outcome (CPC 1 or 2): [5 studies, observational, Kilgannon 2010 2165, Bellomo 2011 R90, Janz 2012 3135, Roberts 2013 2107, Elmer 2014] For the critical outcome of survival to

hospital discharge with favourable neurological outcome (CPC 1 or 2) we have identified very low quality evidence (downgraded as very serious bias and serious inconsistency, indirectness, confounding)) from 5

observational studies with conflicting results [2 showed hyperoxia worse than normoxia]. Studies

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/30/SummarofBiasAssessmentsOrganDonationFinal.xlsx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/30/AgreementDisagreement_Updated_Reasons_final.xlsx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/30/TableResultsFinal.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/30/ILCORDataCollectionFormOrganDonationFinal.xls

reported CPC 1 or 2 outcomes at discharge: • Janz [2012 3135] showed in a single centre study of 170 ICU patients treated with therapeutic hypothermia that the maximum PaO2 in the first 24 h after arrest

was associated with a worse outcome (CPC 1 or 2) (poor neurological status at hospital discharge, adjusted OR 1.485 [95% CI1.032– 2.136] P = .033). • Roberts [2013 2107] showed in a single centre

study of 193 ICU patients that the first PaO2 after ROSC was not associated with outcome (hyperoxia

adjusted OR for poor neurological outcome 1.05 [95% CI 0.45-2.42] P=0.911). • Elmer [2014] showed

in a single centre study of 184 ICU patients that oxygen exposure over first 24 h of ventilation was not associated with outcome with unadjusted and adjusted outcomes [effect size cannot be estimated from

data]. Two studies did not report CPC outcomes, and used other measures as a surrogate marker: • Kilgannon [2010 2165] reported worse independent functional survival at hospital discharge (hyperoxia

vs. normoxia 124/1156 vs. 245/1171 [29 vs. 38%], unadjusted OR 0.45 [95%CI 0.36 -0.58] P 300mmHg in 1st 24 h after arrest) and normoxia (22/49 vs. 25/70, unadjusted OR 0.68 [95% CI 0.32 to

1.44] P=0.31) for 30 day survival or survival to discharge (20/49 vs. 24/70, unadjusted OR 0.76 [95% CI 0.36 to 1.61] P=0.47). • Elmer [2014] reported that of 184 ICU patients, 36 % were exposed to

severe hyperoxia, there overall mortality was 54 %, and severe hyperoxia, was associated with decreased survival in both unadjusted and adjusted analysis [adjusted odds ratio (OR) for survival 0.83

per hour exposure (95% CI 0.69-0.990, P = 0.04]. Survival to ICU discharge: [2 observational studies, Ihle 2013 186, Nelskyla 2013] For the important outcome of survival to ICU discharge we have identified

very low quality evidence (downgraded as very serious bias, serious indirectness, confounding) from 2 observational studies that showed no harm from hyperoxia: • Ihle [2013 186] showed in a data linkage

study of worse PaO2 (highest/lowest) in first 24 on ICU hyperoxia was not associated with outcome (ICU mortality 35% vs. 32% for hyperoxia vs. normoxia, unadjusted OR 1.16 [95%CI 0.56 – 2.40] P=0.68). •

One observational study [Nelskyla 2013, survival to 30 days] enrolling 122 ICU admissions patients that showed no difference between patients with hyperoxia (PaO2 > 300mmHg in 1st 24 h after arrest) and

normoxia (ICU discharge 53% vs. 46%, adjusted OR 0.75 [95%CI 0.36-1.55] P=0.43). 3. Hypoxia vs. normoxia Survival to hospital discharge (or survival to 30 days): [3 observational studies, Kilgannon

2010 2165, Bellomo 2011 R90, Ihle 2013 186] For the critical outcome of survival to discharge (or

survival to 30 days) we have identified very low quality evidence (downgraded as very serious bias and serious indirectness, confounding) from 3 observational studies that showed : • Kilgannon [2010 2165]

showed a worse outcome with hypoxia vs. normoxia based on the first ICU PaO2 (57 vs. 45%, adjusted OR hypoxia exposure 1.3 [95%CI 1.1-1.5] P = 0.009). • Bellomo [2011 R90] showed a hypoxia vs.

normoxia (based on the worse PaO2 in first 24 h on ICU) hospital mortality of 60 vs. 47% (hypoxia/poor O2 exchange vs. normoxia, OR hospital mortality 1.2 (1.1 to 1.4) P= 0.002). This paper also reported

discharge to home outcomes (hypoxia/poor O2 exchange vs. normoxia 26 vs. 24%). • Ihle [2013 186] showed in a data linkage study of worse PaO2 (highest/lowest) in first 24 on ICU no difference in

outcome between hypoxia and normoxia (for in hospital mortality, 51 vs. 41%, adjusted OR hypoxia vs. normoxia 0.93 [95%CI 0.47-1.87]. Survival to ICU discharge: [1 observational study, Ihle 2013 186] For

the important outcome of survival to ICU discharge we have identified very low quality evidence (downgraded as very serious bias and serious indirectness, confounding) from 1 observational study: •

Ihle [2013 186] showed in a data linkage study of worse PaO2 (highest/lowest) in first 24 on ICU hypoxia was associated with a worse unadjusted outcome (ICU mortality 49% vs. 32% for hypoxia vs.

normoxia, unadjusted OR 2.15 [95% CI 1.23 – 3.77] P=0.008). RR 0.74 (95% CI 0.56 -0.96) – worse with hypoxia.



• We recommend the avoidance of hypoxia in adults with ROSC after cardiac arrest in any setting (strong

recommendation, very low quality evidence). • We suggest the avoidance of hyperoxia in adults with ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence). • We

suggest the use of 100% inspired oxygen until the arterial oxygen saturation or the partial pressure of arterial oxygen can be measured reliably in adults with ROSC after cardiac arrest in any setting (weak

recommendation, very low quality evidence).

CoSTR Attachments:

CoS and TR for O2 after ROC_JS3Jan2015.docx

ALS448_OxygendoseafterROSC_JS_3Jan2015.ppt

Oxygen dose during CPR


Full Question:

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/31/CoS%20and%20TR%20for%20O2%20after%20ROC_JS3Jan2015.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/31/ALS448_OxygendoseafterROSC_JS_3Jan2015.ppt

In adults with cardiac arrest in any setting (P), does administering a maximal oxygen concentration (e.g. 100% by face mask or closed circuit) (I), compared with no supplemental oxygen

(e.g. 21%) or a reduced oxygen concentration (e.g. 40-50%) (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only




There are no adult human studies that directly compare maximal inspired oxygen with any other inspired oxygen concentration. For the critical outcome of survival to hospital discharge with favourable

neurological outcome (CPC 1 or 2) we identified very low quality evidence (downgraded for very serious risk of bias and very serious indirectness, and serious imprecision) from 1 observational study

[Spindelboeck 2013 770] enrolling 145 OHCA patients who had a PaO2 measured during CPR that showed no difference between an intermediate PaO2 and low PaO2 [11/83 vs. 1/32, RR 4.2 (95 CI 0.57

– 31.52) P = 0.16], or between a high PaO2 and low PaO2 [7/30 vs. 1/32 RR 7.45 (95 CI 0.98 – 57.15) P = 0.053]. For the important outcome of ROSC we identified very low quality evidence (downgraded for

very serious risk of bias and very serious indirectness, and serious imprecision) from 1 observational study [Spindelboeck 2013 770] enrolling 145 OHCA patients who had a PaO2 measured during CPR that

showed improved ROSC in those with a higher PaO2; [Intermediate PaO2 vs. Low PaO2 47/83 vs. 7/32 RR 2.59 (95% CI 1.31 – 5.12) P = 0.006], [High PaO2 vs. Low PaO2 25/30 vs. 7/32 RR 3.81 (95% CI

1.94 – 7.48) P = 0.0001], [High PaO2 vs. Intermediate PaO2 25/30 vs. 47/83, RR 1.47 (95% CI 1.15 – 1.88) P=0.002]. In the single identified study [Spindelboeck 2013 770] all patients had tracheal

intubation and received 100% inspired oxygen during CPR. The worse outcomes associated with a low PaO2 during CPR could be an indication of illness severity.



We suggest the use of the maximal feasible inspired oxygen concentration during CPR (weak

recommendation, very low quality evidence). In making this recommendation we have considered the limited available evidence, the need to correct tissue hypoxia during CPR, and see no reason to change

the current treatment recommendation, which includes use of 100% inspired oxygen during adult cardiac arrest.

CoSTR Attachments:

ALS 889 OxygenduringCPR_JS3Jan2014.docx O2duringCPR_Soar_TF_30jan2015.ppt

Pregnancy and cardiac arrest

Question Type:


Among pregnant women who are in cardiac arrest in any setting (P), does any specific intervention(s) (I), compared with standard care (usual resuscitation practice) (C), change Survival with Favorable

neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only




We found no comparative studies of doing or not doing uterine displacement for women in cardiac arrest

prior to delivery. We found no comparisons of different maneuvers (e.g., manual displacement vs. left pelvic tilt) to achieve optimal uterine displacement for women in cardiac arrest prior to delivery.

Physiologic reviews and studies of uterine displacement maneuvers in non-arrest populations of pregnant women support that uterine displacement might be physiologically beneficial for women in cardiac arrest

(Cyna AM, Cochrane 2006, CD002251). Any benefit would have to be weighed against the potential interference with usual resuscitation care. For the critical outcomes of survival with favorable

neurological/functional outcome at discharge, 30 days, 60 days, 180 days, AND/OR 1 year, and survival only at discharge, 30 days, 60 days, 180 days, AND/OR 1 year, and the important outcomes of ROSC,

we found three observational studies of 154 subjects collectively (Einav, 2012, 1191, Dijkman, 2010, 282, Baghirzada, 2013, 1077) that provided very low quality evidence comparing cardiac arrest

resuscitation with or without perimortem caesarian section. Procedures to ascertain cases and controls in

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https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/32/O2duringCPR_Soar_TF_30jan2015.ppt

these studies were sufficiently different that the pooled comparison of any of the assigned outcomes would be considered inappropriate.



We suggest delivery for women in cardiac arrest in the second half of pregnancy. (very weak

recommendation, very low quality) There is insufficient evidence to define a specific time interval by which delivery should begin. High quality usual resuscitation care and therapeutic interventions that

target the most likely cause(s) of cardiac arrest remain important in this population. Value and Preferences Statement: In making this statement, we place value on maternal and neonatal survival, on

the absence of data on uterine displacement in women with cardiac arrest, and on our uncertainty about the absolute effect of either uterine displacement or perimortem delivery on any of the assigned

outcomes.

CoSTR Attachments:

Mhyre Zelop Pregnancy Excel Tables 2-9-14.xlsx

ALS 436 Pregnancy - Dallas 1-22-2015.pptx ALS 436 Pregnancy text and endnote 1-15-15.docx

Prognostication in hypothermia

Question Type:


Among adults with ROSC who are treated with hypothermia, (P), does any clinical variable when normal (e.g. 1. Clinical Exam, 2. EEG, 3. SSEP, 4. Imaging, 5. Other) when present (I), compared with

any clinical variable when abnormal (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days,

180 days AND/OR 1 year (O)?



Clinical Examination: In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management, bilaterally absent pupillary reflexes to light at 72 or

later from ROSC predict a poor outcome (death, vegetative state or severe cerebral disability) with very high precision (FPR 0[0-3]%). Bilaterally absent corneal reflexes at 72h or later from ROSC is also an

accurate predictor of poor outcome, but it is less specific (FPR 2[0-7]%). Both these predictors have a low sensitivity (. 25%). Bilaterally absent or extensor motor response to pain at 36h or later from ROSC

has a relatively high sensitivity for prediction of poor outcome (70[65-74]%). However, its false positive rate is also high (10[7-15]%). There are little data at present on combination of clinical signs. Presence

of myoclonus within 72h from cardiac arrest is inconsistently associated with poor outcome (FPR 6%; 95%CIs 3-9). A prolonged, continuous and generalised myoclonus (status myoclonus) within 72h from

cardiac arrest predicts poor outcome with high precision (FPR 0 [0-4[%) but low sensitivity (16%; 95%CIs 11-22). Rare cases of good outcome in patients with an early-onset status myoclonus have been

reported. Predictors based on clinical examination, especially corneal reflex and motor response to pain, may be affected by sedation or paralysis. Blinding of the treating team is very difficult to achieve for

predictors based on clinical examination, which implies a risk of self-fulfilling prophecy. Electrophysiology: In patients who are comatose after resuscitation from cardiac arrest and who are

treated with targeted temperature management a bilaterally absent N20 wave accurately predicts a poor neurological outcome after rewarming (at 72h from ROSC) (FPR 1[0-3]%) while prediction during TTM is

less reliable (FPR 2[0-4]%). Absence of EEG background reactivity during TTM is inconsistently

associated with a poor neurological outcome (FPR 2 [1-7]%) while after rewarming at .72 h from ROSC it predicts a poor outcome with 0[0-3]% FPR. Limitations of EEG reactivity include being operator

dependent and non-quantitative, and lacking standardization. Presence of epileptiform discharges on EEG, both during TH or after rewarming is inconsistently associated with poor neurological outcome.

Presence of electrographic seizures or status epilepticus, either during TTM or after rewarming is almost invariably associated with poor outcome. The definition of epileptiform activity and status epilepticus is

inconsistent among studies. Limited evidence shows that prognosis is worse when status epilepticus is associated to a non-continuous background or absence of reactivity. A flat or low-voltage EEG was

inconsistently associated with poor outcome. Timing and definitions of low voltage was inconsistent among studies. A lowest BIS value =0 during TTM, corresponding to a flat or very low voltage EEG

during TH is inconsistently associated with poor outcome (FPR from 0% to 10%). BIS is affected by

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https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/142/ALS%20436%20Pregnancy%20text%20and%20endnote%201-15-15.docx

interference from muscular artefacts, which restricts its use in patients who are sedated and paralysed during TTM treatment. The amplitude of the EEG signal may be affected on a variety of technical

conditions such as skin and scalp impedance, inter-electrode distances, size, type and placement of the exploring electrodes, and type of filters adopted.49 Use of EEG grading, brainstem auditory evoked

potentials and pain-related somatosensory evoked potentials has been documented only in single studies

and their predictive value needs confirmation from other studies. Biomarkers: In patients who are

comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management, high and increasing concentrations of biomarkers are associated with poor outcome.

However, the biomarkers’ thresholds which predict a poor neurological outcome with 0% FPR vary between studies. Advantages of biomarkers over other predictors such as EEG and clinical examination

include quantitative results and likely independence from the effects of sedatives. Moreover, in most prognostication studies biomarkers were not used as a criterion for WLST (see Table 2). S-100B is less

well documented than NSE. Imaging: In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management the presence of global cerebral

oedema or a reduction of the grey/white matter interface measured as the GWR within 2 hours from ROSC predicted poor outcome with 0% FPR, but the GWR thresholds for 0% FPR varied among studies,

according to the area studied and the measurement technique. In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management the

presence of diffuse hypoxic-ischemic injury detected by DWI changes and quantified by ADC from 2 to 6 days from ROSC predicted poor outcome with 0% FPR. The ADC thresholds for 0% FPR varied among

studies, according to the cerebral area studied and the measurement technique. All studies on prognostication after cardiac arrest using imaging have a small sample size with a consequent low

precision, and are prone to selection bias, since the imaging studies were performed at discretion of treating physician, which may have caused a selection bias and overestimated their performance.

Imaging studies depend partly on subjective human decision in identifying the region of interest to be studied and in the interpretation of results.



Clinical examination:In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management, we recommend using bilaterally absent pupillary light

reflexes or the combined absence of both pupillary and corneal reflexes at .72 h from ROSC to predict poor outcome. We do not suggest using an absent or extensor motor response to pain (M.2) alone to

predict poor outcome, given its high false positive rate. However, due to its high sensitivity, this sign may be used to identify the population with poor neurological status needing prognostication or to

predict poor outcome in combination with other more robust predictors. We suggest using the presence of a status myoclonus within 72 h from ROSC in combination with other predictors for prognosticating a

poor neurological outcome. We suggest prolonging the observation of clinical signs when interference from residual sedation or paralysis is suspected, so that the possibility of obtaining false positive results

is minimized. We recommend that the earliest time to prognosticate a poor neurological outcome is 72hrs after ROSC, and should be extended longer if the residual effect of sedation and/or paralysis

confounds the clinical examination.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. In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management we

suggest using EEG-based predictors such as absence of EEG reactivity to external stimuli, presence of burst-suppression after rewarming or status epilepticus .72h after ROSC in combination with other

predictors for prognosticating a poor neurological outcome. We do not suggest using BIS to predict poor outcome during TTM in patients who are comatose after resuscitation from cardiac arrest and are treated

with targeted temperature management. Qu: ??at the early pahse? Biomarkers:In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature

management we suggest using high serum values of NSE at 48 h-72 h from ROSC in combination with other predictors for prognosticating a poor neurological outcome. However, no threshold enabling

prediction with zero FPR can be recommended. We also suggest using utmost care and preferably sampling at multiple time-points when assessing NSE, to avoid false positive results due to haemolysis.

Imaging:In patients who are comatose after resuscitation from cardiac arrest and who are treated with targeted temperature management we suggest using the presence of a marked reduction of the GM/WM

ratio on brain CT within 2 h after ROSC or the presence of extensive reduction in diffusion on brain MRI at 2-6 days after ROSC in combination with other predictors for prognosticating a poor neurological

outcome. We suggest using brain imaging studies for prognostication only in centres where specific experience is available.

CoSTR Attachments:

Evidence Profiles Table 3b TH.pdf Evidence Profiles Table 3d TH.pdf

Evidence Profiles Table 3c TH.pdf Sandroni Hypothermia TH plenary and TF.pdf

COSTR Draft Prognostication in Hypothermia 2015-3.pdf

Evidence Profile Table 3a TH.pdf

Prognostication in normothermia

Question Type:


Among adults who are comatose after cardiac arrest and are not treated with targeted temperature

management (P), does any clinical finding when normal (e.g. 1. Clinical exam 2. EEG 3. SSEP 4.Imaging 5. Other) (I), compared with any clinical finding when abnormal (C), change Survival with Favorable




Clinical examination: In patients who are comatose after resuscitation from cardiac arrest and who are not treated with targeted temperature management, an absent pupillary reflex to light at 72h from ROSC

predicts poor outcome with high accuracy (0[0-8]% FPR). An absent corneal reflex at 72h from ROSC is also an accurate predictor of poor outcome, but it is less specific (FPR 5[0-25]%). Sensitivity of

prediction is low (18-30%). The accuracy of the combined absence of pupillary and corneal reflexes is

equivalent to that of the absence of the pupillary reflex alone. An absent or extensor motor response to pain (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. In patients who are comatose after resuscitation from cardiac arrest and who are not treated with targeted temperature management presence of myoclonus or status myoclonus within

72h from ROSC predicts a poor outcome with high accuracy (0[0-5]% FPR). However, rare cases of good outcome in patients with an early-onset myoclonus have been reported.48, 49 Blinding of the treating

team is very difficult to achieve for predictors based on clinical examination, which implies a risk of self-fulfilling prophecy. Electrophysiology: In patients who are comatose after resuscitation from cardiac

arrest and who are not treated with targeted temperature management, a bilaterally absent N20 wave within 72h from ROSC predicts a poor outcome with high precision (FPR from 0[0-3]% to 1[0-5]).

Conversely, a delayed or absent N70 SEP from 24h to 72h after ROSC is often associated to false positive predictions. There is a potential risk of self-fulfilling prophecy for predictions based on absent

SSEP results. Unfavourable EEG patterns, such as EEG Grades 3-5 or 4-5, or an EEG below 21 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: In patients who are comatose after resuscitation from cardiac arrest and who are not treated with targeted temperature management, high concentrations of biomarkers predict a poor

outcome. However, the thresholds associated with 0% FPR vary between studies. S-100B is less well documented than NSE. The main reasons for the observed variability in biomarkers’ thresholds include

the use of heterogeneous measurement techniques 53-55, the presence of extra-neuronal sources of biomarkers (haemolysis and neuroendocrine tumors for NSE 56, muscle and adipose tissue breakdown

for S-100B 57), and the incomplete knowledge of the kinetics of their blood concentrations in the first few days after ROSC. Advantages of biomarkers over other predictors such as EEG and clinical

examination include quantitative results and likely independence from the effects of sedatives. Imaging: In patients who are comatose after resuscitation from cardiac arrest and who are not treated with

targeted temperature management the presence of global cerebral oedema or a reduction of the grey/white matter interface, measured as the GWR within 48 hours from ROSC predicts an almost

invariably poor outcome. The GWR thresholds for 0% FPR vary among studies, according to the area studied and the measurement technique adopted. The presence of diffuse hypoxic-ischemic injury

detected by DWI changes and quantified by ADC from 2 to 6 days from ROSC predicts poor outcome with low FPR. The ADC thresholds for 0% FPR vary among studies, according to the cerebral area studied

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https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/33/Evidence%20Profiles%20Table%203d%20TH.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/33/Evidence%20Profiles%20Table%203c%20TH.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/33/Sandroni%20Hypothermia%20TH%20plenary%20and%20TF.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/33/COSTR%20Draft%20Prognostication%20in%20Hypothermia%202015-3.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/33/Evidence%20Profile%20Table%203a%20TH.pdf

and the measurement technique. All studies on prognostication after cardiac arrest using imaging have a small sample size with a consequent very low precision, and are prone to selection bias.



Clinical examination: In patients who are comatose after resuscitation from cardiac arrest and who are

not treated with targeted temperature management, we recommend using the absence of pupillary reflex to light (or the combined absence of both pupillary and corneal reflexes) at ≥72h from ROSC to

predict poor outcome. We do not suggest using an absent or extensor motor response to pain (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: In patients who are

comatose after resuscitation from cardiac arrest and who are not treated with targeted temperature management, we recommend using bilateral absence of the N20 SSEP wave within 72h from ROSC to

predict poor outcome. SSEP recording requires appropriate skills and experience, and utmost care should be taken to avoid electrical interference from muscle artefacts or from the ICU environment. In patients

who are comatose after resuscitation from cardiac arrest and who are not treated with targeted temperature management, we suggest using the presence of burst-suppression on EEG at 72h from

ROSC in combination with other predictors for prognosticating a poor neurological outcome. We do not suggest using EEG grades due to the inconsistencies in their definitions. We also do not suggest using

low-voltage EEG given the potential interferences of technical factors on EEG amplitude. Biomarkers: In patients who are comatose after resuscitation from cardiac arrest and who are treated with therapeutic

hypothermia we suggest using high serum values of NSE at 24 h-72 h from ROSC in combination with other predictors for prognosticating a poor neurological outcome. However, no threshold enabling

prediction with zero FPR can be recommended. We also suggest using utmost care and preferably

sampling at multiple time-points when assessing NSE, to avoid false positive results due to haemolysis. Imaging: In patients who are comatose after resuscitation from cardiac arrest and who are not treated

with targeted temperature management we suggest using the presence of a marked reduction of the GM/WM ratio on brain CT within 48 h after ROSC or the presence of extensive reduction in diffusion on

brain MRI at 2-6 days after ROSC only in combination with other more established predictors for prognosticating a poor neurological outcome. We also suggest using brain imaging studies for

prognostication only in centres where specific experience is available.

CoSTR Attachments:

Evidence Profile Table 3c NT.pdf Evidence Profile Table 3b NT.pdf

COSTR Draft Prognostication in Normothermia 2015 - 2.pdf ALS 713 Prognostication in non-TTM-treated Plenary and TF.pdf

Evidence Profile Table 3a NT.pdf Evidence Profile Table 3d NT.pdf

Pulmonary embolism cardiac arrest


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

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/34/Evidence%20Profile%20Table%203c%20NT.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/34/Evidence%20Profile%20Table%203b%20NT.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/34/COSTR%20Draft%20Prognostication%20in%20Normothermia%202015%20-%202.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/34/ALS%20713%20Prognostication%20in%20non-TTM-treated%20Plenary%20and%20TF.pdf

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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,

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.

CoSTR Attachments:

Percutaneous.pdf

RCT_Subgroup.pdf SurgicalEmbolectomy.pdf

RCT_Gesamt.pdf NonRCT_Gesamt.pdf

Steroids and hormones for cardiac arrest


https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/35/Percutaneous.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/35/RCT_Subgroup.pdf

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Full Question: Among adults who are in cardiac arrest in any setting (P), does corticosteroid or mineralocorticoid

administration during CPR (I), compared with not using steroids (C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only




For in-hospital cardiac arrests: For the important outcome of ROSC (return of spontaneous circulation) there were 2 randomized control trials (Mentzelopoulos 2009,15 & 2013,270) of low quality evidence

(downgraded for indirectness and for imprecision) in 368 patients with in-hospital cardiac arrests. These demonstrated an improved outcome with the use of methylprednisolone and vasopressin in addition to

epinephrine compared with the use of epinephrine and placebo. Mentzelopoulos 2009, found that ROSC was higher in those treated with Vasopressin, Steroids (methylprednisolone) and Epinephrine +/-

hydrocortisone than in those treated with only epinephrine + placebo 39/48 (81.3%) vs 27/52 (51.9%, p< 0.003). Mentzelopoulos 2013, found that ROSC was higher in those treated with Vasopressin,

Steroids (methylprednisolone) and Epinephrine +/- hydrocortisone than in those treated with only epinephrine + placebo: 109/130 (83.9%) vs 91/138 (65.9%), OR 2.98 (95% CI 1.39-6.4, p = 0.005).

When the data were pooled, the overall OR for ROSC was 3.02 (95% CI 1.85-4.93). For the critical outcome of survival to discharge, there was 1 randomized control trial (Mentzelopoulos 2009,15) of low

quality evidence (downgraded for indirectness and for imprecision) in 100 patients with in-hospital cardiac arrest. This showed an improved outcome with the use of methylprednisolone + vasopressin +

epinephrine during cardiac arrest + hydrocortisone post-ROSC for those with shock, compared with the use of only epinephrine and placebo (9/48 = 19% vs 2/52= 4%, p = 0.02). For the critical outcome of

survival to discharge with good neurological outcome, there was 1 randomized control trial (Mentzelopoulos 2013,270) of low quality evidence (downgraded for indirectness and for imprecision) in

268 patients with in-hospital cardiac arrest. This demonstrated improved outcome with methylprednisolone, vasopressin, epinephrine + hydrocortisone in those with post-ROSC shock

compared with those with only epinephrine + placebo [18/130 (13.9%) vs 7/138 (5.1%)], OR 3.28 (95% CI, 1.17 to 9.20; P = 0.02). For out-of-hospital cardiac arrest: For the important outcome of

ROSC, there were 2 studies (Paris 1984,1008, RCT & Tsai 2007, 318, observational study) of very low quality in 183 patients. The RCT (Paris) demonstrated no improvement in ROSC with steroids in cardiac

arrest: 5.4% (2/37) with hydrocortisone achieved ROSC long enough to be admitted to ICU vs 8.7% (4/46) who received placebo. However, the observational study (Tsai) demonstrated apparent benefit:

ROSC in 58% receiving hydrocortisone vs 38% without, p = 0.049. For out- of - hospital cardiac arrests, for the critical outcome of survival to discharge, there were 2 studies (Paris 1984,1008 & Tsai 2007,

318) of very low quality in 183 patients. Both failed to show any benefit with the use of steroids: Paris had no long-term survivors and Tsai demonstrated survival to discharge in 8% (3/36) receiving

hydrocortisone compared with 10% (6/61) receiving placebo, p = 0.805.



For IHCA: For IHCA we suggest that the combination of methylprednisolone, vasopressin & epinephrine may be considered as an alternative to epinephrine alone during CPR (weak recommendation, low quality

evidence). Values and preferences statement: Mortality is high and there are few interventions known to improve outcome from in hospital cardiac arrest, so it is reasonable to consider the use of the triple-

agent drug regime since it would be relatively easy to implement and of low cost. However, a larger, multi-centre randomized control trial to further assess the effect of the use of steroids in cardiac arrest,

both in combination with vasospressin & epinephrine and with epinephrine alone would be useful. For OHCA: We recommend against the routine use of steroids during CPR for OOHCA. Values and preference

statement: There is very little evidence of poor quality from two studies regarding the effect of the

addition of a dose of steroids during out-of-hospital cardiac arrest, but both studies demonstrated no benefit, so the cost of their addition doesn’t seem worthwhile.

CoSTR Attachments:

Summary of Bias Assessments for Use of Steroids in Cardiac Arrest.xlsx

Characteristics of the 2 Studies by Mentzelopoulos 2009+ 13 for AMSTAR.docx GradePro table for Steroids during CPR for OHCA.docx

R ROSC Forest plot.svg GradePro table for Steroids during CPR for IHCA.docx

AMSTARguidelineTool.pdf Final Article selection for Steroids in CA.xlsx

Steroids in CA - ILCORSlideTemplate.Dallas2015.plenary and TF. 1.7.15.ppt Observational Studies on smoking in pregnanch; GradePro.docx

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https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/139/R%20ROSC%20Forest%20plot.svg

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/139/GradePro%20table%20for%20Steroids%20during%20CPR%20for%20IHCA.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/139/AMSTARguidelineTool.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/139/Final%20Article%20selection%20for%20Steroids%20in%20CA.xlsx

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Timing of drug delivery (epinephrine)


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, g3028) of low quality (downgraded for serious risk of bias and upgraded for dose-response effect) in 25,905 in-hospital-

cardiac arrests with a non-shockable rhythm, that demonstrated an improved outcome with early administration of adrenaline : Adjusted OR compared with reference interval of 1-3 min of 0.91 (95% CI

0.82 - 1.00) when given after 4-6 mins , 0.74 (95% CI 0.63 - 0.88) when given after 7-9 mins and 0.63 (95% CI 0.52 - 0.76) when given at > 9 mins after onset of arrest. For in-hospital cardiac arrests, for

the critical outcome of neurologically intact survival at hospital discharge (assessed with CPC ≤ 2), there was one observational study (Donnino 2014,g3028) of low quality (downgraded for serious risk of bias

and upgraded for dose-response effect) in 25,905 in-hospital cardiac arrests with a non-shockable rhythm, that demonstrated an improved outcome from early administration of adrenaline: Adjusted OR

compared with reference interval of 1-3 min of 0.93 (95% CI 0.82 - 1.06) when given after 4-7 mins, 0.77 (95% CI 0.62 - 0.95) when given after 7-9 mins and 0.68 (95% CI 0.53 - 0.86) when given at > 9

mins after onset of arrest. For in-hospital cardiac arrests, for the important outcome of return of spontaneous circulation (ROSC), there was one observational study (Donnino 2014, g3028) of low

quality (downgraded for serious risk of bias and upgraded for dose-response effect) in 25,905 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 IHCA with shockable rhythms.

========= For OOHCA For the critical outcome of survival to hospital discharge, there were four observational studies (Goto 2013,R188, Nakahara 2013,782, Koscik 2013,915 and Stielle 1992,1045) of

very low quality evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision) , enrolling over 420,000 OOHCAs that did not demonstrate any consistent benefit from early

administration of adrenaline : One study enrolling 209,577 OOHCAs (Goto 2013,R188) demonstrated no significant difference in one month survival for shockable rhythms when epinephrine was administered

pre-hospital in < 9min (OR 0.95; 95% CI, 0.77–1.16), 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, 2013, 782) showed improved

outcome (survival) for arrests of cardiac origin, with early pre-hospital epinephrine (< 0.001). Similarly, for arrests of non-cardiac origin, early pre-hospital epinephrine (< 0.001). This benefit held when MVLRA

was done with the primary predictor the total time from call to administration of epinephrine - for arrests of cardiac origin and non-cardiac origin, early pre-hospital epinephrine ( 10 mins - OR 0.91 (95% CI

0.35, 2.37; C-statistic 0.75). However, for PEA, OR 2.35 (95% CI 0.38 -14.7, p = 0.32) for survival with early epinephrine (at < 10mins) compared with epinephrine at > 10 mins. However, for VF early

epinephrine was not associated with any significant beneficial effect OR = 1.52 (95% CI 0.53- 4.40, p=0.41) for survival with early epinephrine (at < 10mins) compared with epinephrine at > 10 mins. For

the critical outcome of neurologically intact survival at hospital discharge (assessed with CPC ≤ 2), there were three observational studies (Goto 2013,R188, Hayashi 2012,1639 & Nakahara 2012,782) of very

low quality evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision and upgraded for a stong association) involving over 261,000 out-of-hospital cardiac arrests that

demonstrated variable benefit from early administration of early epinephrine: One study enrolling 209,577 OOHCAs (Goto 2013, R188) did not show any significant difference in one month CPC 1-2 for

shockable rhythms or non-shockable rhythms with pre-hospital epinephrine administered in < 9 min [aOR 0.71 (95% CI = 0.54-0.92) & 0.95 (0.62-1.37)] compared with no pre-hospital epinephrine.

However, there was a negative association for one month CPC 1-2 with pre-hospital epinephrine given at >10 min: For shockable rhythms with pre-hospital epinephrine at 10-19 min OR= 0.34 (95% CI=0.28-

0.42) & with pre-hospital epinephrine at > 20min OR = 0.21 (95% CI=0.14-0.31); For non-shockable rhythms OR 0.63 (95% CI = 0.48-0.80) & 0.49 (95% CI = 0.32-0.71) for pre-hospital epinephrine

administered at 10-19 and > 20 minutes after arrest. In one study enrolling 3,161 subjects (Hayashi 2012,1639), in VF/VT early pre-hospital epinephrine (at ≤10min from EMS receipt of call to

administration of epinephrine) was associated with improved 1 month neurological outcome compared

with no pre-hospital epinephrine, with a big effect size (OR 6.34 (95% CI 1.49-27.02)), However, later

epinephrine was associated with a worse outcome – epinephrine at 11-20 min aOR 0.65 (95% CI 0.36-1.20) 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 2013,782), for arrests of cardiac origin and non-cardiac origin, early pre-

hospital epinephrine (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 2013, 915) showed that overall, early

epinephrine (10mins after 911 call) with aOR for ROSC of 1.78 (1.15,2.74; C-statistic 0.63). For witnessed arrests, early epinephrine was also associated with improved ROSC - aOR 3.20 (1.75,5.88; C

statistic 0.68)] and for PEA, early epinephrine was associated with improved ROSC, OR 3.45 (1.56,7.62). However, for VF/VT early epinephrine was not associated with significant improvement in ROSC [OR 1.66

(0.83, 3.31)].



For In and Out of HCA with an initial non-shockable rhythm, we suggest that if epinephrine is to be

administered, it is given as soon as feasible after the onset of the arrest (weak recommendation, low quality evidence). Values and preferences statement: In making this recommendation, we place a high

value on being able to modify a current (standard) treatment at minimal cost. For IHCA with an initial shockable rhythm we found insufficient data to make a treatment suggestion regarding the timing of

administration of epinephrine (there were no studies addressing this issue). For In and Out of HCA with an initial shockable rhythm, we found insufficient evidence to make a treatment suggestion regarding the

timing of administration of epinephrine, particularly in relation to defibrillation, and the optimal timing may vary for different groups of patients and different circumstances. Values and preferences statement:

Thought there is insufficient evidence to support a treatment recommendation, we place a higher value on early defibrillation than on administration of epinephrine.

CoSTR Attachments:

R2 Joint CoStar Statement Dec 2014 .docx

Time to Epi. GRADE and study overview IHCA.pdf Summary of Bias Assessments Example and Template.xlsx

Timing of Adminstration of Epinephrine GradePro table Jan 2015.docx

Ultrasound during CPR

Question Type:


Among adults who are in cardiac arrest in any setting (P), does use of ultrasound (including echocardiography or other organ assessments) during CPR (I), compared with standard CPR and

resuscitation without use of ultrasound (C), change Survival with Favorable neurological/functional 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 important outcome of ROSC, we identified one randomized controlled trial investigating the use of cardiac ultrasound use during ACLS, compared to no use of cardiac ultrasound during ACLS in adult

patients with PEA arrest.[Chardoli;2012;287] This study enrolled 100 patients in a convenience sample and reported ROSC for at least 10 seconds in 34% of patients in the US group vs 28% in the group with

no US (p=0.52). The evidence was downgraded for imprecision (small sample size), and very high risk of

bias (no information anout randomization allocation, lack of blinding, lack of blinding in outcome

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/36/R2%20Joint%20%20CoStar%20Statement%20Dec%202014%20.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/36/Time%20to%20Epi.%20GRADE%20and%20study%20overview%20IHCA.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/36/Summary%20of%20Bias%20Assessments%20%20Example%20and%20Template.xlsx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/36/Timing%20of%20Adminstration%20of%20Epinephrine%20GradePro%20table%20Jan%202015.docx

assessors). This evidence was therefore graded as very low quality. For the critical outcome of survival, we identified one observational study.[Prosen;2010;1548] The evidence was downgraded for very high

risk of bias (significant confounding, selection bias) and imprecision (small sample size). Therefore we concluded that the data does not provide enough evidence to address the PICO question.



There is inadequate evidence to evaluate the benefit of cardiac US during ACLS. Based on expert

opinion, we suggest (weak recommendation, very low quality evidence) that if a qualified sonographer is present and cardiac US can be performed without interfering with standard ACLS protocol, it may be

considered as an additional diagnostic tool to identify potentially reversible causes.

CoSTR Attachments:

US.PICO.Presentation.ppt

Vasopressors for cardiac arrest (1. Epi v Placebo)


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



Treatment Recommendation Given the observed benefit in short term outcomes, we suggest Standard Dose Epinephrine be administered to patients in cardiac arrest.(weak recommendation, low quality)

Values and Preferences Statement: In making this statement, we place value on the short-term outcomes of ROSC and survival to admission, and our uncertainty about the absolute effect on survival

and neurological outcome.

CoSTR Attachments:

C2015_Worksheet_ALS_Vasopressors in cardiac arrest Jan 2 2015.docx Epi vs. Placebo.docx

Vasopressors for cardiac arrest (2. Epi vs. high dose Epi)


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



https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/141/US.PICO.Presentation.ppt

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/37/C2015_Worksheet_ALS_Vasopressors%20in%20cardiac%20arrest%20Jan%202%202015.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/37/Epi%20vs.%20Placebo.docx

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.

CoSTR Attachments:

SDE vs. HDE.docx

C2015_Worksheet_ALS_Vasopressors in cardiac arrest Jan 2 2015.docx

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

Question Type:


Among adults who are in cardiac arrest in any setting (P), does use of epinephrine (I), compared with vasopressin (C), change survival to 30 days with good neurological outcome, survival to 30 days, survival

to hospital discharge with good neurological outcome, survival to hospital discharge, ROSC (O)?



We found a single RCT (Mukoyama 2009; 755) n=336 that compared multiple doses of Standard Dose Epinephrine (SDE) with multiple doses of Standard Dose Vasopressin in the Emergency Department after

OHCA. The trial had a high rate of bias as much of the methodology is unclear and there was a 37% post randomization exclusion. The primary outcome measure was CPC score of 1 or 2 however neither the

sample size estimate nor power calculation were included in the paper. There were no significant differences in either critical outcomes of survival to discharge with neurological outcome as defined as

Cerebral Category Performance Score of 1 or 2 (RR 0.68, 95% CI 0.25–1.82, 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).



Treatment Recommendation: We suggest against initiating vasopressin as a substitution for epinephrine in the treatment in cardiac arrest. (weak recommendation, low quality) Values and Preferences

Statement: The recommendation considers the fact that vasopressin is widely used now, and the available data do not indicate any reason to change practice.

CoSTR Attachments:

Epi vs. Vasopressin.docx

C2015_Worksheet_ALS_Vasopressors in cardiac arrest Jan 2 2015.docx

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

Question Type:


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,

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/38/SDE%20vs.%20HDE.docx


https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/39/Epi%20vs.%20Vasopressin.docx


p=0.45] For the important outcomes of survival to admission we found 5 RCTs (Ducros, 2011, 453; Gueugniaud 2008, 21; Lindner 1997, 535;Ong 2012, 953; Wenzel 2004, 105 high quality) n=2438

demonstrating no significant differences in survival to hospital admission with vasopressin epinephrine combination therapy (0.88, 95% CI 0.73-1.06, p=0.17) For the important outcomes of return of

spontaneous circulation (ROSC) we found 6 RCTs (Callaway 2006, 1316; Ducros, 2011, 453; Gueugniaud

2008, 21; Lindner 1997, 535;Ong 2012, 953; Wenzel 2004, 105 high quality) demonstrating no ROSC

advantage with vasopressin epinephrine combination therapy with RR 0.96, 95% CI 0.89-1.04, p=0.31.



We suggest against adding vasopressin to standard dose epinephrine during cardiac arrest. (weak recommendation, moderate quality) Values and Preferences Statement: In making this recommendation,

we considered it distracting and costly to add a drug that has no evidence of additional benefit for patients. We also have no reason to withdraw this drug if the drug is currently in use.

CoSTR Attachments:

Epi vs. Epi Vaso Combo.docx C2015_Worksheet_ALS_Vasopressors in cardiac arrest Jan 2 2015.docx

Ventilation rate during continuous chest compression


Full Question: in adults with cardiac arrest with a secure airway receiving chest compressions (in any setting, and with

standard tidal volume) (P), does does a ventilation rate of 10 breaths/min (I), compared with compared to any other ventilation rate (C), change Survival with Favorable neurological/functional outcome at

discharge, 30 days, 60 days, 180 days AND/OR 1 year, Survival only at discharge, 30 days, 60 days, 180 days AND/OR 1 year, ROSC (O)?



We did not identify any evidence to address the critical outcomes of Survival with favorable

neurological/functional outcome at discharge, 30 days, 60 days, 180 days and, or 1 year Survival at discharge, 30 days, 60 days, 180 days AND/OR 1 year. We identified very low quality evidence

(downgraded for very serious risk of bias and indirectness, and serious inconsistency and imprecision) from 10 animal studies [Sanders 2002 553, Aufderheide 2004 s345, Aufderheide 2004 1960,

Yannopoulos 2004 75, Yannopoulos 2006 1444, Hayes 2007 357, Cavus 2008 118, Hwang 2008 183, Gazmuri 2012 259, Kill 2014 e89] and 1 human non-RCT [Abella 2005 305] that does not enable us to

estimate the effect of a ventilation rate of 10 per minute compared to any other rate for the important outcome of ROSC with confidence.



We suggest a ventilation rate of 10 breaths per minute in adults with cardiac arrest with a secure airway

receiving continuous chest compressions (weak recommendation, very low quality evidence)

CoSTR Attachments:

Ventilation Rate after ROSC_3Jan2015.docx

ALS808_VentilationduringContinousCCILCORSlides_14Dec2014.pptx

Ventilation strategy post resuscitation

Question Type:


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)?



https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/40/Epi%20vs.%20Epi%20Vaso%20Combo.docx


https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/41/Ventilation%20Rate%20after%20ROSC_3Jan2015.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/41/ALS808_VentilationduringContinousCCILCORSlides_14Dec2014.pptx

Hypocapnia No studies have specifically randomised patients to ventilation to a specific PaCO2 goal. For the critical outcome of neurologically intact survival, two very low quality cohort studies {Roberts 2013

2107, Lee 2014 55} with a total of 8,376 patients (downgraded for very serious concerns about risk of bias and imprecision) showed hypocapnia (PaCO2 6.7kPa) One very low quality cohort study {Lee 2014

2107} with a total of 850 patients (downgraded for very serious concerns about risk of bias and

imprecision) showed no difference in outcome for patients ventilated to hypercapnia (>PaCO2 6.0kPa).

One very low quality cohort study {Verhaasalo 2014 1463} with a total of 409 patients (downgraded for very serious concerns about risk of bias and imprecision) showed better outcome for patients ventilated

to hypercapnia (PaCO2 5.1-10.1 kPa). For the critical outcome of of death (or failure to be discharged home), One very low quality cohort study {Schneider 2013 927} with a total of 16,542 patients

(downgraded for very serious concerns about risk of bias and imprecision) showed no difference in patients ventilated to hypercapnia (PaCO2 >6.0kPa) One very low quality cohort study {Lee 2014 2107}

with a total of 850 patients (downgraded for very serious concerns about risk of bias and imprecision) showed a higher mean PaCO2 in survivors.



No studies demonstrate better outcome with ventilation to a specific PaCO2 in patients with ROSC. We

suggest maintaining PaCO2 within a normal physiological range as part of a post-ROSC bundle of care (weak recommendation, very low quality evidence). No studies demonstrate better outcome with

ventilation to a specific PaCO2 in patients with ROSC. Hypocarbia is associated with worse outcome and we suggest should be avoided where possible (moderate recommendation, very low quality evidence).

The upper limit at which PaCO2 becomes harmful is unknown, although mild hypercapnia may have some neuroprotective effect (weak recommendation, very low quality evidence).

CoSTR Attachments:

ILCOR ALS571-post review.ppt ILCOR ALS571-post review Final.ppt

ILCOR ALS571-post review Final.pdf ALS 571 Ventilation to a specific pCO2 or pO2 goal.docx

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/42/ILCOR%20ALS571-post%20review.ppt

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/42/ILCOR%20ALS571-post%20review%20Final.ppt

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/42/ILCOR%20ALS571-post%20review%20Final.pdf

https://volunteer.heart.org/apps/pico/Lists/CoSTRPublicComment/Attachments/42/ALS%20571%20Ventilation%20to%20a%20specific%20pCO2%20or%20pO2%20goal.docx

advanced airway placement

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