AAEM 2015 Resuscitation Articles v11 - FINAL...

2/26/2015

1

AAEMPractice Changing Articles Resuscitation 2014 - 2015

Corey M. Slovis, M.D.Vanderbilt University Medical Center

Metro Nashville Fire DepartmentNashville International Airport

Nashville, TN

VanderbiltEM.com

Cardiac ArrestsEpi

CalciumCPR

Defibrillation

• Does Epinephrine use have true benefits in CPR?

• Meta analysis, 14 RCTs, 12,246 patients

• Studies were:

•Epi vs placebo (1) n = 534

•Epi vs high does Epi (6) n = 6,174

•Epi vs Vasopression (1) n = 336

•Epi vs Epi + Vasopressin (6) n = 5,202

Resuscitation 2014;85:732-40

• Epi vs placebo (1) n = 534 ROSC

• Epi vs High dose Epi (6) n = 6,174

• Epi vs Epi + Vasopressin (6) n = 5,202

• Epi vs Vasopressin (1) n = 336

- No differences in survival or neuro outcome

- No differences in survival or neuro outcome

- No differences in ROSC, admit, survival or neuro

- No differences in ROSC, admit, survival or neuro

ResultsResuscitation 2014;85:732-40

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Benefits of Epinephrine in CPRConclusions and Take Homes

• Very hard to prove efficacy

• Very hard to stop using it

• Epi + Vasopressin + steroids??

• Future studies will hopefully help us defineits role or lack there of

• 1,556 patients from 2000 – 2012

• 1,134 (73%) received epinephrine

• 422 (27%) did not receive epinephrine

• Evaluated frequency of CPC 1 - 2 survival

JACC 2014;64:2360-7

Does prehospital epinephrine improve functional outcome post OOH cardiac arrest?

• Study from Paris, France

• All patients has ROSC

• All were admitted

• + Epi patients: older, less witnessed

• + Epi patients: longer resuscitation, less VF/VT

JACC 2014;64:2360-7

Study compared 228 pairs of Epi vs non-Epimatched samples

0

10

20

30

40

50

60

70

30%

61%

Epi vs No-Epi: CPC 1 - 2Matched Pairs Evaluation

Epi Used No Epi

P < 0.001

68/228

138/228

Epi vs No-EpiAdditional Results

• Longer delay to epi = worse outcomes

• Negative effects of epi across subgroups

• Rhythm, TH, length of CPR, PCI

• The more the epi, the worse the outcome

JACC 2014;64:2360-7

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0.48

0.30

Epi Dosing and SurvivalCPC 1 - 2

1 MG 2 - 5 MGS

0.23

> 5 MGS

OR

JACC 2014;64:2360-7

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Epinephrine in Cardiac ArrestTake Homes

• Use appears to decrease functional neurological

• More epi = worse outcomes

• May increase ischemic-reperfusion and post-

• PCI and hypothermia do NOT attenuate Epi’s

• As usual, more study needed, but epi alone is not

JACC 2014;64:2360-7

status in survivors

anoxic injury

the answer to improved neurologic intact survival

negative effects

Is Calcium Beneficial in Cardiac Arrest?

• Systematic Review Snapshot

• 14 studies, 10 reported ROSC/Survival

• Only 2 were blinded

• 70% were human trials

Annal Emerg Med 2014; 64:187-189

“There is no conclusive evidence that

administration of calcium during CPR

improves survival”

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Take HomesCalcium in CPR

• Do not use routinely

• Consider if hyperkalemia a possibility

• Wide QRS, Renal Failure

• Heart Block/Bradycardia with peaked T waves

Therapeutic Hypothermia

And PCI s/p Arrest

2015 ACC/AHA GuidelinesPCI and Hypothermia

• Therapeutic hypothermia should be started ASAP for all comatose STEMI patients and out of hospital arrests due to VF or VT (1B)

• Immediate PCI is indicated in all STEMI arrest patients including those who are receiving therapeutic hypothermia (1B)

• 754 consecutive comatose patients s/p arrest• 269 (35.7%) VF/VT and got TH• 122 of these got early CCL vs late CCL• 26.6% “no MI” had acute coronary occlusion


Should all VF arrests go to the CCL even if comatose and no STEMI on post arrest 12 lead?

Survival to Hospital Discharge Early CCL in Comatose non STEMI VF/VT

Early CCL

48.6

65.6

Late CCL

28.6

No CCL

p = 0.001

p = 0.007


• ROC Investigators

• 3,981 patients from 151 hospitals

• ROSC > 60 minutes in-hospital


How much does early PCI and TH affects neurologically intact survival

s/p OOH cardiac arrest

2/26/2015

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Patients

• VF 41%, PEA 27%, AS 23%

• TH in 56% of VF; 20% AS

• Early PCI in 77% of VF; 9% AS

• LOC on arrival not available from data

• TH + PCI obviously only in comatose pts


0

10

20

30

40

50

60

70

27.1

18.4

Hypothermia + PCI

No PCI No TH

30.3

21.9


%

Survival SurvivalGood Neuro Good Neuro

63.4

53.0

PCI + TH

Survival Good Neuro

TH and PCITake Home

Be careful that a “non-STEMI” is not an acutely intervenable AMI

1- = 30% of VF/VT arrests without STEMI will have an acute, stentable lesion

S/P VF/VT awake PCI

S/P VF/VT coma PCI + TH

2015 Management of VF/VT Survivors

• 31,292 ALS vs 1,643 BLS cases

• Medicare billing data records (20% of total)

• Harvard study 2009 – 2011, no rural serviced

• Propensity matching utilized

JAMA 2014, online Nov 24, 2014

Is ALS significantly better than BLS for out of hospital cardiac arrest?

ALS younger, more male, less likely to have chronic medical condition and picked up at a residence

BLS more likely to be picked up at a skilled nursing facility

Used data based on protocol that BLS was dispatched if ALS not available

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6

0

2

4

6

8

10

12

14

16 13.1%

9.2%

Survival to Hospital DischargePropensity Matched

BLS ALS

RR = 1.443% diff


0

10

20

30

40

50

21.8%

44.8%

Poor Neurologic Outcome – Admitted PtsPropensity Matched

BLS ALS

(95% CI = 18.6 – 27.4)


0

1

2

3

4

5

6

7

8

9

10

9.6%

6.2%

30 Day to SurvivalPropensity Matched

BLS ALS

RR – 1.595% CI = (1.2 – 1.7)


Probability of Survival

BLS vs ALS Take Homes

• AEDs and O2 by BVM are key

• How important is ALS?

• Not a randomized study

• Many potential confounders

• What’s the importance of the peri-shock pause?

• 2,006 patients with pre/post shock times

• Evaluated ∆T pre-shock and post shock

• Compared survival to discharge


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• 29% of pts had pre-shock pause > 20 seconds

• Median ∆T to shock was 15 seconds

• 6.5% had a post-shock pause > 20 seconds

• Median ∆T to resume CPR was 6 seconds

Resuscitation 2013;3:336-42 Optimal pre-shock pause is < 10 seconds

< 10 sec vs > 20 sec increases survival (OR = 1.5)

• Does compressing during defibrillator

• 129 patients, Canadian study

• 54.2% received compressions during charging

• No significant change in rate or depth noted


charging (CDC) improve compression fractionand/or survival?

Pre Shock Pause

STD CPR

3.5 Sec

15 Sec

CDC CPR

P < 0.001


Conclusions on CDC

• Easy to teach and do

• Increases compression fraction by 10%

• Not yet clear if improves survival

• Larger study will evaluate mortality effects

• AEDs will all soon have this feature

Peri-shock PausesTake Homes

• Be ready to shock before stopping CPR

• Stop CPR and shock near simultaneously

• Hands on CPR?

• Post shock interval is not as important

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• Is hands-on defibrillation safe?

• Cadaver study; 6 cadavers used

• Used A-P defibrillator pad placement

• Defibrillated cadavers at 360 joules

Resuscitation 2014; epub ahead of print

Dry Abrasion-Dry H2O 1/10 NSS NSS Gel

Conclusions

Based on this study, hands-on defibrillation is dangerous and should not be done

Or

Based on this study, cadavers should not defibrillate themselves


Study Issues

• Used cadavers without blood and perfused organs

• Measured current on cadaver body surface

• Did not directly measure current going to rescuer directly

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This is the first hands-on defibrillation study not to use hands-on defibrillation


Take Homes onHands-On Defibrillation (HOD)

• The safety of hand-on defibrillation (HOD) is not fully known

• Use gloves if you do HOD

• Do not put your hands on the pad(s)

• Large “real life” study needed

• HOD or not, minimize pre-shock pause

Early ResuscitationFor Sepsis

Early Goal Directed Therapy (EGDT) is a quality metric to be

used to judge ED physician expertise

Does it make a difference? • 1,391 patients from 31 US EDs

• Protocol based PROCESS trial; 3 groups

• 439 EGDT, 446 Protocol, 456 Usual

• Evaluated 90 day and 1 year mortalities

• Evaluated multiple other parameters

New Engl J Med 2014;370:1683-1693

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• 500cc bolus for hypotension

• CVP catheter to CVP > 8 mm Hg

• Vasopressors for SBP < 90 mm Hg

• Dobutamine if SVO2 < 70%

• RBCs if Hct below 30 %

EGDT Protocol CareNew Engl J Med 2014;370:1683-1693

• 500 cc repeat NSS boluses

• CVP catheter insertion > 8mmHg

• Vasoactive infusion SBP > 90 mmHg

• Iontropic agent if SVO2 < 70%

• RBCs to HCT > 30%

EGDT Protocol CareNew Engl J Med 2014;370:1683-1693

• CVP not required

• Up to 2,000cc if SBP < 100

• Pressors only if SBP < 100 s/p 2L

• RBCs only if Hgb < 7.5g/dl

Protocol Care New Engl J Med 2014;370:1683-1693

• Fluids until MD felt perfusion adequate

• Pressors as needed by MD

Standard TherapyNew Engl J Med 2014;370:1683-1693

0

500

1000

1500

2000

2500

3000

3500

4000

2800

3300

Fluid Resuscitation

EGDT Protocol

2300

Usual

P < 0.001

New Engl J Med 2014;370:1683-1693

0

10

20

30

40

50

60

54.4% 52.2%

Vasopressor Use

EGDT Protocol

44.1%

Usual

P = 0.003

New Engl J Med 2014;370:1683-1693

2/26/2015

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0

5

10

15

20

25

30

35

40

21.0

31.9

Survival in PROCESS TrialIn Hospital and 90 Day

EGDT Protocol

18.2

30.8

In-Hosp In-Hosp90 D 90 D

New Engl J Med 2014;370:1683-1693

UsualIn-Hosp 90 D

18.9

33.7

P = NS

• 1,600 patients ARISE Trial

• Australasian Resuscitation in Sepsis Eval

• 765 EGDT, 804 Usual Care

• Volume, Pressors, RBCs Compared

• 90 day outcomes Evaluated

New Engl J Med 2014;371:1496-1506

EGDT vs STD Therapy

Volume Pressor

cc

57.8%

EGDT EGDTSTD STP

RBCsEGDT STD

13.6%

7.0%

P < 0.001 for all

1964cc

1713cc 66%

cc

0

2

4

6

8

10

12

14

16

18

2018.6%

EGDT vs STD Therapy90 Day Mortality

EGDT STD RX

18.8%

P = NS

New Engl J Med 2014;371:1496-1506

%

• Besides no difference in 90 day survival

• No difference in in-hospital mortality

• No difference in LOS

• No difference in organ support

Additional ResultsNew Engl J Med 2014;371:1496-1506 • No benefits to routine CVP

• No benefits to aggressive pressor use

• No benefits from early transfusion

• Transfuse for Hgb < 7.5g/dl

• Be aggressive with fluid and early ABX

Protocol Care in SepsisTake Homes

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STROKE• 1,700 randomized prehospital patients• MgSO4 within 2 hours of stroke• 4 grams MgSO4 in 15 min; 16grams/24hrs

New Engl J Med 2015;372:528-30

Is magnesium neuroprotective in stroke?

Magnesium offers NO benefits

• 500 patients from the Netherlands• Mechanical therapy vs control with TPA• 89% Rxd with TPA pre-randomization• Used retrievable stents (81.5%)

New Engl J Med 2014;372:11-20

Can a mechanical therapy improve outcome in CVA patients who have distal carotid or

proximal MCA or proximal ACA occlusion?All patients had distal internal carotid or proximal

MCA (M1, M2) or ACA (A1, A2) lesions

The Mr CLEAN Trial

New Engl J Med 2014;372:11-20

Rankin Score

0 No symptoms

1 No clinically significant disability

2 Slight disabilities- - - - - - - - - - - - - - - - - - - - - - - - - -

3 Moderate disabilities

4 Moderately severe disabilities

5 Severe disabilities

6 Death0123456789

1011121314

6%

Modified Rankin Score 0 – 1 at 90 days0 = no sx, 1 no clinical disability

Control Group Mechanical Rx

11.6%

OR = 2.06(1.08 – 3.92)

New Engl J Med 2014;372:11-20

2/26/2015

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0

5

10

15

20

25

30

35

40

19.1%

Modified Rankin Score 0 – 2 at 90 days2 = slight disability, can look after self, not at baseline

Control Group Mechanical Rx

32.6%

OR = 2.05(1.36 – 3.09)

New Engl J Med 2014;372:11-20

There was a 13.5% absolute increase in the

likelihood of having a 0 – 2 modified Rankin

Score at 90 days

Mr. Clean TrialComments

• Authors note that second generation retrievable stents are superior to first generation Merci device – one that failed to improve outcomes when added to TPA

• 9% of interventional group embolized

• 13% underwent carotid stenting

Adding Intraarterial Treatment to TPATake Homes

• Results are encouraging and suggest this therapy may become mainstream

• Single study from the Netherlands

• Control group in this study did not do as well as in other TPA studies

• If you can walk and care for yourself with a 13.5% increased chance, lets study it more

• Treatment within 12 hours of symptoms

• Proximal anterior occlusion, small infarct core

• Moderate to good collateral circulation

• IV TPA post CT/CTA perfusion study

New Eng J Med 2015; epub ahead of print

Does mechanical thrombectomy improve outcomes in acute stroke patients who have also

received TPA – The ESCAPE Trial

2/26/2015

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• 316 patients, 22 centers

• Canada, US, S. Korea, Ireland, UK

• Thrombectomy via available devices

• Retrievable stents recommended

• Suction through catheter in carotid

New Eng J Med 2015; epub ahead of print New Eng J Med 2015; epub ahead of print

All patients received TPA with or without use of mechanical device

Study stopped before planned 500 patients due to MR. CLEAN findings and efficacy

in first 300 ESCAPE subjects

Rankin Score

0 No symptoms

1 No clinically significant disability

2 Slight disabilities- - - - - - - - - - - - - - - - - - - - - - - - - -

3 Moderate disabilities

4 Moderately severe disabilities

5 Severe disabilities

6 Death0

10

20

30

40

50

60

29.3%

90 Day Good Neurologic Outcomes(Rankin 1 -2)

TPA TPA + Mechanical

53.0%

P < 0.001

%

New Eng J Med 2015; epub ahead of print

2/26/2015

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There was a 23.7% absolute increase in the

likelihood of having a 0 – 2 modified Rankin

Score at 90 days

OR=2.6

P < 0.001

Mechanical Device in StrokeTake Homes

Based now on 2 different studies, it appears

that TPA plus mechanical therapy will

become the standard of care unless a new

trial shows harm

• 434 EMS patients with monitored VF or VT

• 75% shocked vs 25% initially thumped

• 16.5% (17 patients) responded to thump

• 57.8% of defibrillated immediate ROSC


How effective is a precordial thump in patients with VF or VT?

0

10

20

30

40

50

60

70

80

90

83.5

16.5

Response to Precordial Thump (n = 103)

9.7

1.9

%

No Response

DeteriorationResponse VF - VT


4.9

ROSC

Precordial ThumpTake Homes

• Rarely works (1/8)

• 2x deteriorate vs improve

• ROSC rare

• Dramatic, for TV, real life, not so much

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• 9,136 ROC CPR patients

• Mean depth of compression 41.9mm

• Evaluated survival on compression depth

Circulation 2014;epub Sept 24

Is the current AHA CPR guideline of >50mm (2in.) compression depth correct?

Survival increased per each 5mm increase in compression depth

Maximum survival benefits achieved by 45.6mm (1.8 inches)

BUT

“Maximize survival was in the depth interval of 40.3 – 55.3mm (peak 45.6)

suggesting that the 2010 AHA CPR guideline target may be too high”

The Authors Conclude:Circulation 2014;epub Sept 24

1.8 inches – 2 inches

NOT more NOT less

Depth & CompressionsTake Homes

Beta Blockers

CPR

2/26/2015

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Annals of Emerg Med 2014, epub ahead of print

Is immediate Beta-Blocker again indicated in acute STEMI care?

Circulation 2013;128:1495-1503

• 270 STEMI patients; STEMI < 6 hours

• Killip Class I or II; no III or IV

• 5mg Q 5 min IV metoprolol (n = 131)

• Oral metoprolol s/p PCI

• MRI evaluation at 5 -7 days (n = 220)

Circulation 2013;128:1495-1503

0

5

10

15

20

25

30

35

g32

Infarct Size(Grams of Infarct)

Control

25.6

Metoprolol

p = 0.012

Circulation 2013;128:1495-1503

• LV EF by 2.67% with BB

• No increase in adverse effects

• No in heart failure or heart block with BB

• No in mortality with BB

Other Findings

Circulation 2013;128:1495-1503

0

5

10

15

20

25

30

35

12.3%

Composite Index(Death, VF/VT, Shock, AV Block, Re-AMI)

Control

7.1%

Metoprolol

p = 0.21

Circulation 2013;128:1495-1503

%

• Anterior AMI subset analysis

• 147 patients from METOCARD-CNIC Trial

• Prehospital IV metoprolol 5mg Q5 x 3 doses


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0

5

10

15

20

25

30

35

40

g34

Infarct Size(Grams of Infarct)

Control

23.4

Metoprolol

- 30% infarct sizep = 0.09


0

5

10

15

20

25

30

35

17.8%

Composite Index(Death, VF/VT, Shock, AV Block, Re-AMI)

Control

6.8%

Metoprolol

%


- 11.1% absolutep = 0.31

Acute IV Beta Blockade in STEMITake Homes

• “Clinically Significant” reduction in infarct size and composite endpoints but not statistically significant

• MDs administered in EMS units

• Was Killip I and II by MD exam

• Not yet a practice changer

• But coming??

• Retrospective ED study

• All EMS to ED arrivals

• All s/p 3 shocks, 3 doses Epi, 300mg Amio

• Compares Esmolol vs no Esmolol


Is Esmolol effective in refractory VF/VT?

0

10

20

30

40

50

60

70

80

33%

66%

Esmolol for Refractory VF/VTSustained ROSC and Good Neuro D/C

Sustained ROSC Good Neuro D/C

10.5%

50%

No NoEsmolol Esmolol


• Very small study

• But impressive results

• Certainly not harmful

• Has been suggested for 50 years

• I think worth a try

BB For Refractory VF/VT

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• Small study

• 25 patients: 9 received Esmolol

• Loaded with .5mg/kg

• Maintained at 0 - .1mg/kg/min

• 4/6 had ROSC Cath lab

• Two of theses 4 had STEMI


Does Esmolol help terminate the “Electrical Storm” of VF?

• 300 PCI patients with STEMI

• 95 patients (32%) received morphine

• Evaluated incidence of vomiting

• Measured platelet inhibition

Circ Cardiovasc Inter 2015;8 epub Jan

Morphine

15%

2%

No Morphine

Vomiting With and Without Morphine

P = 0.001

Circ Cardiovasc Inter 2015;8 epub Jan

Morphine

53%

29%

No Morphine

High Residual Platelet Activity(P2Y12 > 208)

P = 0.0001

Morphine in AMITake Homes

• Morphine increases vomiting in AMI

• Decreases platelet inhibitor absorption

• Platelet aggregation affected by morphine

• Try to use fentanyl and antiemetics

• If you use morphine – less and antiemetics

TXA

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• 1217 Level 1 trauma patients

• All required immediate OR or blood

• TXA 1 gram IV then 1 G over 8 hours

• 54% penetrating trauma, 25% TBI

• Evaluated mortality in 150 TXA matched pts

J Trauma and Acute Care 2014;76:1373

• August 2009 – January 2013

• 80% SBP < 120 mm Hg

• 30% SBP < 70mm Hg

• ¾ required surgery and transfusion

• Evaluated mortality in 150 TXA matched pts


No TXA

27%

17%

TXA

Mortality TXA vs Standard Care

P = 0.024


Use new drugs as soon as possible

Before they develop side effectsor loose efficacy

• Groups “perfectly matched”

• TXA group received more fluids, RBCs and FFP in OR

• If the death within 2 hours patients excluded then:

• Changes 81 deaths to 61 total deaths


No TXA

27%

17%

TXA

TXA vs No TXADeaths in 2 hrs exlcuded

P = 0.024


2/26/2015

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TXA Summary 2014 - 2015

• Role in US Level I Centers Unclear

• Seems to work if transport to definitive

• Studies over next 12-18 months will be more definitive

care will be delayed significantlyTXA 2015

• Prehospital antifibinolytic coagulopathy and hemorrhage study PATCH Study

• Australian study

• Currently underway

• Evaluates TXA for EMS use

Emerg Med Australia 2014;26:194-7

A randomized TXA study in high morbidity – high mortality Australian and New Zealand patients

• US Department of Defense trial

• Will use TXA during air evacuations

• Placebo-controlled, randomized

• Rochester NY, Pittsburg, Utah and San Antonio

• < 2 hrs of injury, < 90 SBP, HR > 110

• 3 dosing regiments

Prehosp Emerg Care 2014; early online

STAAMP TrialTXA During Air Medical Prehospital Transport

TXA Summary

• Proven on battlefield

• Proven in 3rd world countries

• Role is soon to be clarified

• Data appears “somewhat” convincing

• Don’t be too sure either way

Lytic Therapy for PE

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• 1,083 PE patients divided into 3 groups

• Used prior 2874 pts derivation cohort findings

• 30 day follow-up; Spanish study

• Hypotensive patients excluded

Chest 2015; online Jan 29

Evaluates BOVA Score for predicting complications from symptomatic PE

BOVA Score

Variable Points

Systolic BP 90 – 100mmHg 2Cardiac Troponin elevation 2RV dysfunction (CT or US) 2HR > 110 1

Stage 1 = 0-2 Stage II = 3-4 Stage 3 = >4

0

5

10

15

20

25

30

35

40

45

50

4.4

18

PE Related Complications and Mortality

PE Complications

47

3.1

1 32 1

PE Mortality2 3

6.810

%

Chest 2015; online Jan 29

• Meta-analysis, 16 trials, 2,115 pts, 1970-2014

• 10% Low risk, 71% Intermed, 1.5% High risk

• 1,499 Intermediate risk patients evaluated

• Assessed morbidity and major bleeding

• Urokinase, streptokinase, TPA, TNK used

JAMA 2014;311:2414-2421

Intermediate Risk defines as a

Hemodynamically stable PE

with RV dysfunction

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0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5 3.89%

MortalityHeparin vs Lytics in PE

Heparin Thrombolytic

2.17%

P = 0.01

JAMA 2014;311:2414-2421

0

1

2

3

4

5

3.04%

Recurrent PE


1.17%

P = 0.003

JAMA 2014;311:2414-2421

0

1

2

3

4

5

6

7

8

9

10

3.42%

PEMajor Bleeding


9.24%

P < 0.001

JAMA 2014;311:2414-2421

0

0.5

1

1.5

2

0.19%

Risk of ICH

Heparin Lytic

1.46%

P = 0.002

JAMA 2014;311:2414-2421

0123456789

1011121314

3.65%4.10%

Age 65 and OlderMortality and Major Bleeding

Heparin Lytic

2.08%

12.93%

Mortality MortalityBleed Bleed

p = 0.07p < 0.001

JAMA 2014;311:2414-2421

2/26/2015

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0

1

2

3

4

5

6

4.29%

2.27%

Age Younger Than 65Mortality and Major Bleeding

Heparin Lytic

2.32%2.84%

Mortality MortalityBleed Bleed

p = 0.09p = 0.89

JAMA 2014;311:2414-2421

• 1,005 patients, 76 sites, 13 countries

• Randomized, double blind, placebo controlled

• Full dose TNK + UFH vs UFH only

• Intermediate risk PE patients

• Death or hemodynamic collapse at 7 days

NEJM 2014;370:1402-11

• PE by CTA (94.9%)

• All patients normotensive

• All had RV dysfunction

• All had Troponin elevation

Intermediate Risk Patients

NEJM 2014;370:1402-11

Efficacy: TNK vs Placebo in PE

Death

5.6

1.6

2.6

5.0

Hemodynamic Collapse

TNK Placebo TNK Placebo

NEJM 2014;370:1402-11

P = 0.02 P = 0.002

Safety: TNK vs Placebo in PE

30 d all cause mortality

1.8

11.5

1.2

2.4

MajorBleeding

TNK Placebo TNK Placebo

NEJM 2014;370:1402-11

P = NS

P < 0.001

2.0

0.2

TNK Placebo

P = 0.003

HemorrhagicShock

%

Thrombolytics for Intermediate Risk PETake Homes

• Hemodynamically stable PE pts with RV dysfunction have decreased mortality with thrombolytic therapy

• Lytic therapy, however, dramatically increases major bleeding and ICH, especially in pts 65 yo and older

• All PE pts should have RV dysfunction and troponin evaluated

• If CTA shows significant clot, plus there is RV dysfunction, plus troponin is positive: patients should be considered for lytic therapy based on age, comorbidities and bleeding risks

• Half dose TNK should always be considered

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• Multicenter, randomized trial

• 59 patients with PE by CT, RV > LV

• IV UFH vs 10 - 20mg TPA by EKOS

Circulation 2014;129:479-86

Is ultrasound-assisted catheter directed thrombolysis superior to IV heparin for

intermediate-risk PE?

Submassive PEsConsider Lytic Therapy in PE

• Refractory Hypoxia or Hypotension

• Young healthy patient

• Large clot burden by CT

• Positive Troponin

• RV > LV by Ultrasound

• Change in RV size (RV/LV ratio)

• Death

• Major Bleeding

• Minor Bleeding


Study Outcomes

0

0.2

0.4

0.6

0.8

1

1.2

1.41.20

1.17

RV/LV Ratio at 24 HoursEKOS vs UFH in PE

UFH

1.280.99

RV/LV

+ = 0 + = 024 hrs 24 hrs

EKOS

p = 0.31 p < 0.001

• No death from PE in either group

• No major bleeding in either group

• 3 minor EKOS bleeds vs 1 with UFH


Additional Results

EKOS For PETake Homes

• No large study yet

• Appears safe in small study

• Appears to improve RV/LV dysfunction

• Unclear if truly superior long term

• EKOS vs 1/2 dose TNK … one day

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Oxygen TherapyIs too much oxygen bad?

Is 100% O2 sat wrong?

• 184 post CPR patients treated with O2

• Hyperoxia vs Prob Hyper, vs Normal vs Hypoxia

• Used Utsein co-variates and multiple repressions

• UPMC Presbyterian Hospital

Intens Care Med 2015;41:45-59

( >300 vs 100 – 299 vs 60 – 100 vs <60mm Hg)

• Measured hours of hyperoxia (O2 > 300mm Hg)

• Overall survival to discharge 46%

• 36% of patients had hyperoxia; x = 1.4hrs (+ 2.2h)


• Hyperoxia = Sequential Organ Failure

• Each Hyperoxia hr Survival by an OR of 0.84

• “Probable” Hyperoxia not Deleterious


Results

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

1.10.84

1.01

Odds of Survival to Discharge

0.74

Hyperoxia( >300)

Hypoxia( <60)

Mod – Prob(101 – 299)

1.01

Normal(60 – 100)


p = 0.02

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• Reviews 14 studies, 8 full, 6 abstracts

• 49,951 patients

• Hyperoxia defined as Pa O2 > 300mm


Do we need to be vigilant about preventing both Hypoxia and Hyperoxia?

Hyperoxia was associated with a 40%

increase ( OR = 1.40) in hospital mortality


Am Heart J 2012;163:334-345

• Results presented late 2004 at AHA

• From Melbourne Australia

• Air vs O2 in MyocarDial Infarction

Is O2 in STEMI Harmful?

Am Heart J 2012;163:334-345

• 441 EMS STEMI patients

• O2 vs no O2 1:1

• All went to PCI

• O2 vs no O2 continued during PCI

• Evaluated at 72 hours and 6 months

Methods

Am Heart J 2012;163:334-345

• Infarct size by CK

• Mean peak Troponin

• ST segment resolution

• Survival

• Death, MI, CVA, Revasc at 6 months

Endpoints

AVOID ResultsAt Hospital Discharge

• Recurrent AMI 5.5% 0.9% (p < 0.01)

• Stroke 1.4% 0.4% (p < 0.30)

• Major Bleed 4.1% 2.7% (p < 0.41)

• Sig. Arrhythmia 40.4% 31.4% (p < 0.05)

• ECG ST Resolution 62.0% 69.6% (p < 0.10)

O2 No O2

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AVOID ResultsAt 6 Months

• Recurrent AMI 7.6% 3.6% (p < 0.07)

• Stroke 2.4% 1.4% (p < 0.43)

• Repeat Revasc 11.0% 7.2% (p < 0.17)

• MACCE 21.9% 15.4% (p < 0.08)

O2 No O2

??? 2015 “Supplemental O2 therapy in patients with STEMI but without

hypoxia increased myocardial injury, recurrent AMI and major

cardiac arrhythmia and was associated with larger AMI”

AVOID Results

So does AVOID prove that you should not give supplemental O2 to

STEMI patients?

0

1

2

3

4

5

6

7

1.8%

4.5%

Mortality in AVOID

O2 No O2

At DischargeO2

At Six Months

3.8%

5.9%

No O2

P = 0.32

Am Heart J 2012;163:334-345

P = 0.11

• Get O2 to 94 – 95%

• Enough is enough

• More to Come

• No more ignoring “great” sats

• No more:“100% O2 by NRB”

O2 in STEMITake Homes

• Hyperoxia for any length of time in bad

• Avoid 100% O2 sats ASAP

• Damage appears time dependent

• Hyperoxia increases mortality and MOSF

Oxygen Take Homes

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• No study has shown a benefit from hyperoxia

• Increasing number of studies and a

• Never be at 100% O2 by pulse ox

• Aim for 93 – 95%

• 89 – 92% or COPD

Hyperoxia Take Homes

meta-analysis show harm Living Forever

Living Forever

• Eat more fish, less red meat

• Drink 1 – 2 glasses of wine or ETOH

• Consume less saturated fats and fried foods

• Eat more nuts

• Exercise?

• Does running affect mortality?

• How far to get what benefit?

• 55,137 patients, 15 years follow-up

• Used medical hx questions of leisure activities

• Divided runners in quintiles < 51 min/wk -

JACC 2014;64:472-81

>176 min/wk

• Used Cooper Clinic of Dallas, TX patients

• Most college educated, white, socio economic

• Ages 18-100, M/F, mean age 44 at baseline

• Excluded prior MI, CVA, cancer

JACC 2014;64:472-81

0

10

20

30

40

50

45.9

17.8

Runners vs Non-RunnersDeath Rate (Deaths/yr/10,000 patients)

Non-Runners Runners

31.7

8.0

All Cause All CauseCard Card

JACC 2014;64:472-81

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Take Homes

• Running reduces all cause mortality by 30%

• Running reduces cardiac mortality by 45%

• Findings consistent even if running just 51 min/week

• Can run 1-2x/week slowly for benefits ( < 10 min miles)

Benefits overcame smoking, HT, HL, obesity

Average in lifespan = 3 years

Running increasing distances and/or atfaster pace does not increase life more!

Do something physical!

Walking is safe and is highly beneficial

Summary

Hands on chest - maybe

Beta Blockers: more

Take all VF/VTs to PCI

Minimize CPR pauses

Summary

TPA plus Mechanical Therapy in Stroke

Lytics work in PE, but beware

Oxygen: not too much, or at all

Be aggressive in sepsis, not with EGDT

Epi and CaCl in arrests cautiously

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