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Year in Review 2014: Critical Care Medicine

Eric J. Seeley, M.D., F.C.C.P. Assistant Professor of Medicine

Division of Pulmonary and Critical Care Medicine

University of California, San Francisco

Disclosures

• I receive laboratory support from CytoVale Diagnostics for research on early sepsis diagnostics

• I am a co-site PI for Pulmonx and PneumRx bronchoscopic lung volume reduction studies

Why I Selected These Studies…

• Rigorously conducted large RCTs

• They were published in major journals

• They answer common “Yeah, buts…”

There are many “Yeah but’s” when it comes to key therapies in CCM

– “Yeah, but in the EGDT trial (Rivers), it was unclear if RBCs

and ScvO2 guided therapy helped and wasn’t it single center trial with a COI involving the Edward’s catheter?”

– “Yeah, but in a septic patients with low albumin, subgroup analysis suggests that albumin resuscitation has a mortality benefit (SAFE Trial).”

– “Yeah, but in patients who are hypertensive at baseline, shouldn’t we target a higher MAP goal?”

– “Yeah, but wasn’t there a study in the NEJM that suggests

a mortality benefit to thrombolysis in sub-massive PE”

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• Rivers EGDT NEJM 2001

– Single center study of 263 pts

– Mortality in EGDT 30.5% vs 46.5%

– Widely “adopted” in clinical practice – Kind of…

– Adopted into the surviving sepsis guidelines

• All of these unanswered ?s led to ProCESS

“Yeah, but in the EGDT trial (Rivers), it was unclear if RBCs and ScvO2 guided therapy helped and wasn’t it single center trial with a COI involving the Edward’s catheter?”

NEJM 2014

• Multicenter, RCT in US – 31 ERs, 1341 Patients with Septic Shock

• 2 SIRS + SBP < 90 despite fluid or lactate > 4

– Randomized to 1 of 3 protocols in first 6 hours 1.Early Goal Directed Therapy (EGDT)

- River’s protocol (ScVO2, Blood, Dobutamine)

2.Protocol-Based Standard Therapy - River’s light (CVC as needed, less blood, no ScVO2 goal)

3.Usual Care - What ERs in academic centers usually do

Shock Index = HR/SBP

EGDT Protocol Protocol Based – STD Rivers “light”

No CVP Hct >21

No ScvO2 goal

Vs.

Edwards Catheter Hct >30

Dobut if ScvO2<70%

What Actually Happened?

Central Line Insertion Scv02 Monitoring

IVF Volume

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NEJM 2014

No Difference in 60 day or 1 year cumulative mortality

Take away… - No need for:

• Edwards Catheter (put next to the PA-Catheter)

• Transfusion goal of Hct >30% (Hct 21 better)

• Dobutamine guided by ScvO2

•Central line NOT ESSENTIAL for hemodynamic

monitoring (i.e. CVP probably as bad as we think)

March 18, NEJM 2014 ALBIOS Study Investigators (Caironi, Gattinoni)

• “Yeah, but in septic patients with low albumin, subgroup analysis suggests that albumin has a mortality benefit” • SAFE trial (2004): NS vs. 4% Albumin in Critically Ill

• Severe sepsis subgroup – lower risk of death but p > 0.05

– ALBIOS Study Design

• 100 ICUs in Italy, 1818 pts with severe sepsis/septic shock

• 20% albumin and crystalloid vs. crystalloid alone

• Target was Albumin > 30 g/L (3.0 g/dL)

• Primary outcome was death at 28 days

March 18, NEJM 2014 ALBIOS Study Investigators (Caironi, Gattinoni)

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March 18, NEJM 2014 ALBIOS Study Investigators (Caironi, Gattinoni)

Take Away… •Hard to justify added expense of Albumin for sepsis resuscitation

March 18, NEJM 2014 ALBIOS Study Investigators (Caironi, Gattinoni)

SEPSISPAM Investigators* NEJM March 2014

“Yeah, but in patients who are hypertensive at baseline, shouldn’t we target a higher MAP goal?” Surviving sepsis guidelines recommend •MAP > 65 in patients with septic shock •Based on human/animal studies of lactate and RBF Trial Design •Multi-center RCT in French ICUs •776 patients with septic shock •Randomized to MAP > 65 vs. MAP > 85

SEPSISPAM Investigators* NEJM March 2014

>85

>65

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SEPSISPAM Investigators* NEJM March 2014

P=0.57

SEPSISPAM Investigators* NEJM March 2014

P=0.57

You could consider higher MAP goals in patients with chronic HTN who are at low risk for afib.

JAMA April 2014

But it’s not all bad news…

101,064 patients in Australia/NZ with severe sepsis/septic shock

JAMA April 2014

But it’s not all bad news…

101,064 patients in Australia/NZ with severe sepsis/septic shock

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How do we treat submassive PE?

Heparin +/- Thrombolytics?

How do we treat submassive PE?

Heparin Heparin +/-

Thrombolytics?

PE

How do we treat submassive PE?

Heparin Heparin +/-

Thrombolytics?

PE

Massive PE: Heparin + Thrombolytics

How do we treat submassive PE?

Heparin Heparin +/-

Thrombolytics?

Sub-massive/ Intermediate PE Therapy Unclear

PE

Massive PE: Heparin + Thrombolytics

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“Yeah, but there was a study in the NEJM that suggest a mortality benefit to thrombolysis in sub-massive PE”

Konstantinides NEJM 2002 MAPPET-3 Trial

Event = Composite End Point

***Composite Primary End-point driven only by secondary thrombolytics******

• Multi-center RCT in Europe

• 1005 patients with Intermediate Risk-PE

– HD Stable with RV dysfunction and + trop

• Randomized to:

– Tenectaplase + Heparin vs. Heparin alone

• Primary Outcome

– Death or hemodynamic collapse 7 days after txt

NEJM 2014 PEITHO investigators

Stroke Patients, 8/10 were >70 yo. Youngest was 65, 4/10 survived

Conclusions: Ending the “Yeah, buts…”

• For Septic Patients

– You can do away with ScvO2 and CVP guided therapy

– There is no benefit to a higher Hb goal in EGDT

– No benefit to Albumin in sepsis resuscitation

– No benefit to MAP > 85 except in chronic HTN

• For Intermediate/Submassive PE

– Probably better to start with Heparin and thrombolyse for hemodynamic decompensation • (ie. Only for massive PE)

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Questions?