1. Evolving Trends in Cardiac Arrest
Michael W. Donnino, MD
Emergency Medicine and Critical Care
Director of the Center for Resuscitation Science
Beth Israel Deaconess Medical Center

2. Disclosures
Research Grants: AHA, NIH, Kaneka, General Electric, Bristol-Myers Squibb
American Heart Association (paid consultant as well as volunteer)
2015 ACLS guidelines editor (paid)
Member, Research Task Force and Clinical – GWTG
Member, ACLS task force for ILCOR

3. The 2015 ACLS Guidelines Focused update
ILCOR  GRADE  AHA/ERC writing groups
The path forward  ongoing continuous update

4. Changes to ACLS Guidelines
Assessment sequence
Chest compression rate and depth
Advanced airway ventilation rate
Targeted temperature management
Vasopressors for resuscitation: vasopressin and epi
Consideration of ECPR (not routine but in certain settings)
Consideration of ETCO2 as one element of determining when to stop resuscitative efforts
Neuroprognstication at 72 hours post TTM
Timing of C-section “modifier”
In this section we are concentrating on those guidelines updates that affect the 2010 ACLS course content and materials.
We will look at each of these in depth, and then address how you add this information to your courses.
Reiterate bullet points

5. Philosophy of Changes
Keep things simple  removal of vasopressin from algorithms, change in respiratory rate to avoid a range
Recognize differences between arrest scenarios:
IN-hospital and OUT-of-hospital arrest  some split recommendations, change in chain of survival, assessment sequence flexibility
Different management for shockable and non-shockable
More formalized and critical evaluation of the studies with GRADE approach and push to “try” to take a stand one way or another though often difficult…

6. New AHA Adult Chains of Survival
1/30/2018
New AHA Adult Chains of Survival
IN-HOSPITAL
(note new
Surveillance and
Prevention link)
One thing that you will see in new course materials will be 2 separate adult chains of survival.
Different pathways of care are distinguished, one for the patient who experiences cardiac arrest in the hospital for those in an out-of–hospital setting. Note that for the in-hospital setting, surveillance and prevention of arrest is the first link (this is similar to the prevention link that is the first link in the pediatric out-of-hospital chain of survival)
IHCA: surveillance & there is an opportunity to prevention; recognition & activation of emergency response; immediate high-quality CPR, rapid defibrillation, advanced life support and postarrest care
OHCA: recognition & activation of emergency response; immediate high-quality CPR; rapid defibrillation ; basic and advanced medical services; advanced life support and postarrest care.
OUT-OF-HOSPITAL,
Including EMS

7. Philosophy of Changes
Keep things simple  removal of vasopressin from algorithms, change in respiratory rate to avoid a range
Recognize differences between arrest scenarios:
IN-hospital and OUT-of-hospital arrest  some split recommendations, change in chain of survival, assessment sequence flexibility
Different management for shockable and non-shockable
More formalized and critical evaluation of the studies with GRADE approach and push to “try” to take a stand one way or another though often difficult…

8. Today – Controversies and Emerging Data
Epinephrine in Cardiac Arrest
Amiodarone, Lidocaine, or Placebo
“Targeted Temperature Management”
Neuroprognostication post-arrest
In this section we are concentrating on those guidelines updates that affect the 2010 ACLS course content and materials.
We will look at each of these in depth, and then address how you add this information to your courses.
Reiterate bullet points

9. Coronary Perfusion Pressure
CPP = Aortic Pressure - Right Atrial Pressure (CPP = Coronary Perfusion Pressure)

11. (Niemann 1986)

12. Epinephrine Versus Placebo
“Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of ROSC.”
Epi group 3.4 times more likely to achieve ROSC than placebo
Jacobs et al. Resuscitation 82 (2011)

13. Epinephrine Versus Placebo
Pre-hospital ROSC: 8.4% (placebo) vs 23.5% (epinephrine)
ED to hospital admission: 13% (placebo) vs 25.4% (epinephrine)
Hospital discharge: 1.9% (placebo) vs 4% (epi) [NS] (50% relative reduction in mortality though not enough patients for statistical significance – thus, caution with interpretation of “negative” trial)
Epi group 3.4 times more likely to achieve ROSC than placebo
Jacobs et al. Resuscitation 82 (2011)

14. VF/VT versus PEA/asystole
Epi group 3.4 times more likely to achieve ROSC than placebo
Jacobs et al. Resuscitation 82 (2011)

15. VF/VT versus PEA/asystole
3.7% %
Epi group 3.4 times more likely to achieve ROSC than placebo
Jacobs et al. Resuscitation 82 (2011)

16. Time To Epinephrine – PEA/Asystole
(Donnino et al. British Medical Journal 2014 )

17. Time To Epinephrine – PEA/Asystole
(Donnino et al. British Medical Journal 2014 )

18. Time To Epinephrine – PEA/Asystole
(Donnino et al. British Medical Journal 2014 )

19. Time To Epinephrine – PEA/Asystole in pediatrics
Figure 3. Time to epinephrine and survival
(Andersen et al., JAMA, 2015)

20. VASopressors for resuscitation: EPINEPHRINE
Administer epinephrine as soon as feasible after the onset of cardiac arrest due to an initial nonshockable rhythm
Association between early administration of epinephrine and increased ROSC, survival to hospital discharge, and neurologically intact survival
2015 (New): It may be reasonable to administer epinephrine as soon as feasible after the onset of cardiac arrest due to an initial nonshockable rhythm.
Why: A very large observational study of cardiac arrest with nonshockable rhythm compared epinephrine given at 1 to 3 minutes with epinephrine given at 3 later time intervals (4 to 6, 7 to 9, and greater than 9 minutes). The study found an association between early administration of epinephrine and increased ROSC, survival to hospital discharge, and neurologically intact survival.
Additional Information
This will not lead to a change in the algorithm. This is a reiteration of an intervention we previously recommended, as we now have new evidence on this.

22. Very Early Epinephrine in VF/VT)
Early administration of epinephrine in patients with cardiac arrest and initial shockable rhythm. Andersen LW, Kurth T, Chase M, Berg KM, Cocchi MN, Callaway C, Donnino MW; BMJ ;353

23. Epinephrine Conclusions
Controversy: Epinephrine “not proven” and may be harmful or counterproductive
Current Guidelines:
PEA/asystole  early and every 3-5 min (Class IIb)
VFIB/VT  after the second defibrillation
MY opinion: Maybe it depends – timing, context, alternative options/etiology of arrest may all factor in…However, I don’t think anyone should die without epinephrine

24. Amiodarone Vs. Lidocaine
Survival to Hospital Discharge??
No Difference but not powered for this
Amiodarone 5% vs. Lidocaine 3% (p = NS)
(Dorian et. al. NEJM)

25. Amiodarone vs. Lidocaine
Bottom Line: Amiodarone currently has “the nod” but the study was small and had some flaws including provision of lipoprotein with deleterious effects to lidocaine group. Thus, giving lidocaine is acceptable alternative

26. Amiodarone vs. Lidocaine
Bottom Line: Amiodarone currently has “the nod” but the study was small and had some flaws including provision of lipoprotein with deleterious effects to lidocaine group. Thus, giving lidocaine is acceptable alternative
Being reproduced with a Phase III trial

27. Amiodarone vs. Lidocaine
Bottom Line: Amiodarone currently has “the nod” but the study was small and had some flaws including provision of lipoprotein with deleterious effects to lidocaine group. Thus, giving lidocaine is acceptable alternative
Currently, being reproduced with very large trial

28. Amiodarone vs. Lidocaine

29. Amiodarone vs. Lidocaine
45.7% % %

30. Amiodarone vs. Lidocaine
24.4% % 21%
45.7% % %

31. Amiodarone Conclusions
Controversy: New study with amio/lido/placebo
Current Guidelines:
Amiodarone may be considered for VF/pVT that is unresponsive to CPR/defib/vasopressor (Class IIb)
Lidocaine may be considered as an alternative to amiodarone for VF/pVT that is unresponsive to CPR/defib/vasopressor therapy (Class IIb)
My opinion: Amiodarone and lidocaine are probably equivalent and slightly better than placebo BUT this study has not yet vetted through the ILCOR/AHA…

32. IV versus IO – does it matter?
What is the current recommendation?
What do you currently do?

33. IV versus IO – Uh, Oh… What is the current recommendation?
What do you currently do?

35. Well, not everyone was happy…

36. Well, not everyone was happy…

37. Well, not everyone was happy…

38. 2010 AHA Recommendations
Treatment Recommendation 1: “We recommend that comatose (i.e., lack of meaningful response to verbal commands) adult patients with ROSC after out-of-hospital VF cardiac arrest should be cooled to 32oC to 34oC for 12 to 24 hours”
(Class I, LOE B)

39. 2010 AHA Recommendations
Treatment Recommendation 2: “Induced hypothermia also may be considered for comatose adult patients with ROSC after out-of-hospital cardiac arrest with an initial rhythm of pulseless electric activity or asystole”
(Class IIb, LOE B)

40. Targeted Temperature Management (TTM)
1 - Should we perform TTM?
- Shockable versus non-shockable rhythms
- Out-of-hospital versus in-hospital
2 - If so, what temperature should we choose?
3 - If so, when should we start? Prehospital?
4 - How long should we go?
5 – What do we do about fever after TTM is done?

41. Targeted Temperature Management (TTM)
1 - Should we perform TTM?
- Shockable versus non-shockable rhythms
- Out-of-hospital versus in-hospital
2 - If so, what temperature should we choose?
3 - If so, when should we start? Prehospital?
4 - How long should we go?
4 – What do we do about fever after TTM is done?

43. Mortality
Neurologic

44. Study Limitations 1 – Non-blinded assessors
2 – One “pseudo-randomized”
3 – Unclear attention to temp management in the control arm
4 – No report of longer term neuro outcomes or granular neurologic outcomes

45. (Strong recommendation, low quality evidence)
ILCOR Recommendation
We recommend TTM as opposed to no TTM for adults with OHCA and initial shockable rhythm who remain unresponsive after return of spontaneous circulation.
(Strong recommendation, low quality evidence)

46. (Weak recommendation, low quality evidence)
ILCOR Recommendation
We suggest TTM as opposed to no TTM for adults with OHCA and initial non-shockable rhythm who remain unresponsive after return of spontaneous circulation.
(Weak recommendation, low quality evidence)

47. (Weak recommendation, low quality evidence)
ILCOR Recommendation
We suggest TTM as opposed to no TTM for adults with IHCA and any initial rhythm who remain unresponsive after return of spontaneous circulation.
(Weak recommendation, low quality evidence)

48. (Weak recommendation, low quality evidence)
ILCOR Recommendation
We suggest TTM as opposed to no TTM for adults with IHCA and any initial rhythm who remain unresponsive after return of spontaneous circulation.
(Weak recommendation, low quality evidence)
*** 2015 AHA stronger for this population with Class I recommendation for all post-arrest patients regardless of rhythm and regardless of in-hospital versus out-of-hospital status

49. Targeted Temperature Management (TTM)
1 - Should we perform TTM?
- Shockable versus non-shockable rhythms
- Out-of-hospital versus in-hospital
2 - If so, what temperature should we choose?
3 - If so, when should we start? Prehospital?
4 - How long should we go?
5 – What do we do about fever after TTM is done?

50. 33 degrees vs 36 degrees 950 Enrolled 473 (33 degrees)
Mortality 235 (50%)
Mortality 225 (48%)
p = 0.51

51. 33 degrees vs 36 degrees 950 Enrolled 473 (33 degrees)
Mortality 235 (50%)
Mortality 225 (48%)
p = 0.51

52. EQUALLY MATCHED GROUPS
33 degrees vs 36 degrees
950 Enrolled
EQUALLY MATCHED GROUPS
473 (33 degrees)
466 (36 degrees)
Mortality 235 (50%)
Mortality 225 (48%)
p = 0.51

53. 33 degrees vs 36 degrees 950 Enrolled EQUALLY MATCHED GROUPS
Mortality 235 (50%)
Mortality 225 (48%)
Median Time BLS: min [0-2] min [0-2]
p = 0.51

54. 33 degrees vs 36 degrees 950 Enrolled 473 (33 degrees)
Mortality 235 (50%)
Mortality 225 (48%)
p = 0.51
Nielsen et. al Targeted Temperature Management at 33 versus 36 degrees after cardiac arrest. New England Journal of Medicine (2013)

55. Other Differences Hypotension criteria Rhythm inclusion differences
Sedation/NMB strategies
Targeted temperature control for 3 days (no fevers in all patients both groups in latest study)
Follow-up protocol for neuro-prognostication

56. Survival Curve Differences

57. Temperature Differences

58. Temperature Differences

59. Other Differences Hypotension criteria Rhythm inclusion differences
Sedation/NMB strategies
Targeted temperature control for 3 days (no fevers in all patients both groups in latest study)
Follow-up protocol for neuro-prognostication

60. (Strong recommendation, moderate quality evidence)
ILCOR Recommendation
We recommend selecting and maintaining a constant target temperature between o Celsius for those for whom TTM is being used.
(Strong recommendation, moderate quality evidence)

61. Theoretical Complications from TTM
1 – Bleeding – no increase in the RCTs but…
2 – Infection (Pneumonia) – trend toward increase
3 – Bradycardia – occurs but is this harmful?
4 – Hypokalemia – yes, increased incidence

62. Targeted Temperature Management (TTM)
1 - Should we perform TTM?
- Shockable versus non-shockable rhythms
- Out-of-hospital versus in-hospital
2 - If so, what temperature should we choose?
3 - If so, when should we start? Prehospital?
4 - How long should we go?
5 – What do we do about fever after TTM is done?

63. Prehospital Hypothermia Trials
3551 Assessed

67. Re-arrest post-ROSC (26% versus 21%) p = 0.008

68. Re-arrest post-ROSC (26% versus 21%) p = 0.008
Pulmonary Edema (41% versus 30%) p < 0.001

69. (Strong recommendation, moderate quality evidence)
ILCOR Recommendation
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)

70. Targeted Temperature Management (TTM)
1 - Should we perform TTM?
- Shockable versus non-shockable rhythms
- Out-of-hospital versus in-hospital
2 - If so, what temperature should we choose?
3 - If so, when should we start? Prehospital?
4 - How long should we go?
5 – What do we do about fever after TTM is done?

71. (Weak recommendation, low quality evidence)
ILCOR Recommendation
We suggest that if TTM is used, duration should be at least 24 hours as done in the two largest previous RCTs.
(Weak recommendation, low quality evidence)

72. Targeted Temperature Management (TTM)
1 - Should we perform TTM?
- Shockable versus non-shockable rhythms
- Out-of-hospital versus in-hospital
2 - If so, what temperature should we choose?
3 - If so, when should we start? Prehospital?
4 - How long should we go?
5 – What about fever after TTM is done?

73. (Weak recommendation, low quality evidence)
ILCOR Recommendation
We suggest prevention and treatment of fever in persistently comatose adults after completion of TTM between 32 and 36o Celsius.
(Weak recommendation, low quality evidence)

74. Keeping the Doctors Away Might Be Among One of the Most Important Post-Cardiac Arrest Interventions

75. Keeping the Doctors Away Might Be Among One of the Most Important Post-Cardiac Arrest Interventions
Non-TTM: 72 hours post-ROSC
TTM: It is reasonable to wait 72 hours post return of normothermia before undergoing neuroprognostication

76. Case 1
65 year old male history of recent CABG surgery is on the hospital floor on POD #4
A nurse obtaining vital signs witnesses the patient become unresponsive and ashen and calls for help…

77. Case 1

78. Case 2
60 year old male presents with respiratory distress secondary to pneumonia and is intubated without complication (ETT confirmed by auscultation, end-tidal, and CXR)
Patient initially stable after intubation with fluids/antibiotics and on low dose of vasopressors
However, 2 hours later, nurse calls for help and…

80. Case 3
66 year old female who presents with hypotension, urosepsis, and acute renal failure
5.6 90 13
191
133 80
3.3

81. Case 3

82. Conclusions
ACLS guidelines have stepped into a new era of continuous review and online fluidity
Epinephrine may be a double-edged sword and should be differentially considered in terms of timing depending on the initial cardiac rhythm
Amiodarone and/or lidocaine may have benefit over placebo for refractory VF/VT, however one does not appear superior to the other

83. Conclusions
IO ”may” need to be carefully looked at in term of efficacy of drug delivery during arrest (specifically amiodarone or lidocaine)

84. Conclusions
END