Hot Topics.

FFICM Preparation Day London March 9th 2016

Rob Mac Sweeney

http://bit.do/CCR-FFICM16

Paul Young | Wellington

Saline or PlasmalyteIs SPLIT the Solution

Hot Topics

•2016

•2015

•2014

•2013

•2012

•Major Research

•Major Guidelines

Major Research Studies2016

Sepsis 3DefinitionsProcess

Delphi ProcessDatabase validation

Screening with qSOAFIdentify with SOAF? Advance

DIABOLOFrench multi-centre RCTEarly metabolic alkalosis382 patients

No separation MV | pH | PaCO2

↔ duration ventilation↔ duration weaning↓ bicarb & days with alkalosis

Major Research Studies2015

HEATParacetamol is harmful ?1g IV Paracetamol 6° or placebo700 ptsGroups well balanced↔ temperature (0.2°C)↔ ICU free days (23 v 22)Immunomodulatory effect ?

PROPPRPragmatic multicentre RCT680 severely ill trauma patients1:1:1 with 1:1:2 FFP / Plt / RC↔ mortality:

Day 1Day 30

Reduced exsanguination

deaths1:1:2 group “caught up”

SPLITCluster, crossover RCT0.9% Saline vs Plasmalyte2,278 ptsAll fluid administrative

purposes2000 ml each↔ AKI 9.2% v 9.6%Pilot study

EUROTHERM> 20 mmHg for > 5 minutes32°C – 35°C vs standard mgtStage 2 387 patients∆ 2.14°C | ↓ stage 2 failure acOR 1.53 poor outcome GOS-

ETiming of intervention ?

ABLEIs fresh blood better than old ?Young RBCs vs standard RBCs2430 patientsRBCs: 6 days vs 22 days90 day mortality: 37% vs 35%No 2° outcome differencesTRIGGER | RECESS

EPO-TBIEPO pleotropic effects40,000 IU EPO x 3 or placeboWithholding criteria606 patients↔ GOS-E 1 - 4: 44% vs 45%↔ 6/12 mortality 11% vs 16%↔ DVT 16% vs 18%

ProMISeOpen label, pragmatic RCTEarly septic shock

EGDT: SpO2 | ScvO2 | CVP |

MAP | Hb1,260 patientsSome separation↔ 90 day mortality: 29% vs

29%

FLORALIOpen label, multi-centre RCTFM vs HFNO vs NIVSpO2 > 92%310 patients↔D28 reintubation 47 v 38 v

50%↓ ICU mortality 19 v 11 v 25%↓ D90 mortality 23 v 12 v 28%

3SitesOpen label, RCT 10 French ICUs

Subclavian v I Jugular v FemoralCRBSI & symptomatic DVTExperienced clinicians3,471 catheters in 3,027 patients1.5 v 3.6 v 4.6 per 1000 cath

dayMechanical Complications

2.1% v 1.4% v 0.7%

Amato StudyPost hoc review of 9 RCTsMultilevel Mediation AnalysisFunctional Lung SizeΔP = (Pplt – PEEP) = (Vt

/CRS)

Vt / Pplat / PEEP →ΔP

ΔP 7 cmH20 = ↑41% mortality

Requires validation

Chlorhexidine BathingPragmatic, Cluster Randomized Crossover study

9340 patientsOnce daily 2% chlorhexidine2 x 10 week periods each↔ infections

55 vs 602.86 vs 2.90 / 1000 pt days

Major Research Studies2014

ALBIOSMulticentre Open Label RCT1795 patients with sepsis /

shock20% albumin + crystal vs crystalTarget serum albumin > 30g/l↔ 28 day mortality

Albumin: 31.8% vs 32%↔ 90 day mortality

Albumin: 41.1% vs 43.6%

ARISE Australian / NZ RCTEGDT vs Usual CareRivers algorithm1600 patients with septic shock↔ 90 mortality

EGDT 18.6% vs 18.8%EGDT - ↑ fluids, vasopressors,

RC, dobutamine

ProCESSAmerican multicentre RCT Testing Rivers EGDT protocolEDGT vs Standard vs Usual

care1341 patients with septic shock↔ day 60 mortality

21% vs 18.2% vs 18.9%↔ day 90 or 1 year mortality

CALORIES Pragmatic, open label RCTEnteral vs Parenteral nutritionCould be fed by either route2400 emergency ICU pts↔ Day 30 mortality

PN: 33.1% vs EN: 34.2%PN – less hypos or vomiting

– no effect on infection

CIRC Mechanical CPR vs Manual CPRUSA / European - OOHCA4753 randomized, 522 excluded↔ ROSC: 28.6% v 32.3%↔ 24 hour survival: 21.8% v 25%↔ Hosp discharge: 9.4% vs 11%

LINC European open label RCTMechanical CPR & defibrillation2589 OOHCA patients↔ 4 hr survival: 23.6% vs 23.7%↔ CPC 1-2 survival

At ICU / Hospital dischargeAt 1 or 6 month

HARP-2 Multicentre, UK/Ireland RCTSimvastatin vs Placebo540 patients with ARDS↔ Ventilator-free days↔ Non-pulmonary organ

failure -free days↔ 28 day mortality

METAPLUS European multi-centre RCT301 pts expected ventilated >3/7Immune enhancing nutrientsHigh protein diet both groups↔ new infections (53% vs 52%)↑ 6/12 mortality with IMN

54% vs 35%

PEITHO European Multi-centre RCT1,006 pts intermediate risk PETenecteplase & heparin vs

placebo & heparin↓ Death / CVS decompensation

2.6% vs 5.6%↔ Deaths: 1.2% vs 1.8%;

P=0.42↑ Stroke: 2.4% v 0.2%; ↑

Bleeding

SEPSISPAMMulti-centre open label RCT776 pts with septic shockMAP 80 - 85 vs 65 – 70↔ D28 mortality 36.6% vs 34%↔ D90 mortality 43.8% vs 42.3%↔ serious adverse event↑ AF with higher BP↑ RRT with lower BP chronic

HTN

TRISSEuropean multi-centre RCT1005 pts septic shock & anaemiaTransfuse Hb <9 g/dl vs <7 g/dlLess blood given (median 4 vs 1)↔D90 mortality (45% vs 43%)↔ischaemia / adverse events

VITdAL-ICUAustrian single centre RCT492 white ICU pts Vit D deficientVit D vs Placebo↔ Hosp LOS 20 vs 19 days↔ Hosp / 6/12 mortalitySeverely deficient subgroup

↓ Hosp mortality 28% vs 46%↔ mortality at 6 months

Major Research Studies2013

TTM StudyMulti-centre RCT

950 OOHCA Patients

33°C vs 36°C

↔ All cause mortality

50% vs 48%

↔ Poor neuro function

54% vs 52%

Kim StudyPrehospital cooling

1,359 OOHCA patients

↔ Survival to hosp discharge

VF 63% vs 64%

nonVF 19% vs 16%

↔ Good neuro recovery

VF 57% vs 62%

nonVF 14% vs 13%

CATIS Study4,071 patients

Within 48 hrs ischemic stroke

Nonthrombolysed and ↑SBP

↑ BP Rx vs no BP Rx

BP control effective

↔ death and major disability

• 14 days / hosp discharge

• 3 months

INTERACT2Early ICH & ↑SBP

SBP <140 mmHg vs <180

2,839 pts

Aggressive BP control lead to

Trend for adverse events

↓ modified Rankin scores

↔ mortality

CRISTAL Stratified, open label RCTAny colloid vs any crystalloid2857 pts with hypovolaemic shock↔ 28 day mortality

25.4% vs 27%Less deaths with colloids at D90

30.7% vs 34.2%Less vasopressors / ventilation

TracMan909 intubated patients

Tracheostomy timing

≤ 4 days vs > 10 days

↔ Mortality / ICU LOS

↔ Complications

Only 45% late group received trache

β Blockade in Septic Shock154 septic pts with ↑HR & ↑dose

NA

Esmolol vs standard Rx

Esmolol

↓ HR / lactate / Norad / Fluids

↑ SVI / LVSWI

↓ D28 mortality (49% vs 80%)

STATIN-VAP300 patients suspected VAP

Simvastatin 60 mg vs placebo

Study stopped early for futility

↔ 28 mortality

↔ Duration MV

↔ Δ SOFA

↑ mortality in statin naïve

21.5% vs 13.8%; p=0.054

VSE Study 268 cardiac arrest ptsAdrenaline/Vasopressin/Methylpred

acutely & hydrocortisone later

VSE associated with improved

ROSC (84% vs 66%)

Good neuro recovery

14% vs 5%

21% vs 8%

(post resuscitation shock)

PROSEVA466 patients with severe ARDS

Prone vs supine position

Prone position associated with

↓ mortality D28: 16% vs 33%

↓ mortality D90: 24% vs 41%

↓ cardiac arrests

↔ complications

VILLANEAU• 921 pts with upper GI bleed

• Hb <7g/dL vs Hb <9g/dL transfusion

triggers

• Restrictive strategy:

• ↓ number of pts receiving

transfusion (15% vs 51%)

• ↑probability survival

• ↓ Less rebleeding / AEs

REDOXS1,223 pts with MOF

Glutamine & antioxidants

Glutamine:

↑ mortality

D28 (34% vs 27%; p=0.05)

D90 (44% vs 37%; p=0.02)

Antioxidants ineffective

↔ Mortality / Other endoints

OSCILLATE 548 pts with moderate-to-severe

ARDS

Trial terminated early

↑mortality 47% vs 35%

HFOV associated with

↑ sedation requirements

↑ neuromuscular blockade

↑ vasopressor support

OSCAR795 pts with moderate-to-severe

ARDS

↔ Mortality 41% vs 41%

↔ Duration antimicrobials

↔ Duration pharmacological

vasoactive support

↔ LOS ICU or Hospital

CRICS452 ventilated pts

No gastric volume monitoring

• ↔VAP (15.8% vs 16.7%)

• ↔ ICU-acquired infections

• ↔ Duration MV / ICU or Hospital

LOS

• ↑calorific goal (OR 1.77)

SUNSET-ICUSingle-centre, block, randomised

trial

Resident nighttime intensivist

↔ ICU LOS

↔ Mortality

↔ Other endpoints

Early Parenteral Nutrition

Early PN versus starvation

1,372 patients

Standard group: 40 % unfed

↔ 60 day mortality

↔ LOS – ICU or Hospital

PN: ↓ duration ventilation

ReversalRetrospective observational

Looked at 10 years of NEJM

publications

Medical reversals – current practice

inferior to a prior standard

146/363 studies

40%

Major Research Studies2012

EN vs EN & PN305 critically ill patients

Day 3 & received <60% calorific goal

EN plus PN to achieve 100% calorific

target vs EN alone

EN plus PN associated with

↑ Calories: 28 vs 20 kcal/kg

↓ Infection: 27% vs 38%

Best TRIP324 pts severe TBI

ICP guided vs clinical and imaging

guided management

↔ Composite of functional &

cognitive measures

↔ 6 month mortality (ICP

39% vs C&I: 41%)

↔ Length of stay

CARRESS

SLEAP Study423 pts

Protocolised sedation vs PS plus daily

sedation break

↔ Time to extubation

↔ ICU LOS / Hospital LOS

↔ Delirium / Unintended

extubations

PS & DSB: ↑sedation / nursing

CHEST study7000 ICU pts

Fluid resuscitation with

6% HES 130/0.4 vs 0.9% saline

↔ Mortality (HES 18% vs 17%)

↔ LOS – ICU / Hospital

HES associated with increased

↑ RRT (7% vs 5.8%; RR 1.21)

↑ Pruritus / Rash / Liver failure

6S Study804 severe sepsis pts

Fluid resuscitation

130/0.4 HES vs Ringer's acetate

HES associated with

↑ D90 death (51% vs 43%)

↑ RRT (22% vs 16%)

↑ bleeding (10 v 6%,p=0.09)

IABP-II Study600 pts with acute MI & cardiogenic

shock

IABP vs no IABP

↔ D30 death (IABP 40 v 41%)

↔ Time to CVS stabilisation

↔ ICU LOS

↔ Catecholamines therapy

PROWESS SHOCK Study1,697 pts with septic shock

↔ 28 day mortality

APC 26.4% vs 24.2%

↔ 90 day mortality

34.1% vs 32.7%

No subgroup effect seen

Berlin Definition of ARDS

MASH-21,204 pts within 4 days of

aneurysmal SAH

MgSO4 (64 mmol/day) vs placebo

↔Functional outcome

↔90 day mortality

MgSO4 26% vs 25%

PRODEX / MIDEXMIDEX (n=500)

Dexmedetomidine v Midaz

Dexmedetomidine:

↓ duration ventilation

↑ patient interaction

↑ hypotension / bradycardia

↔ time at target sedation

↔ ICU / Hosp LOS / death

PRODEX / MIDEXPRODEX (n=437)

Dexmedetomidine v Propofol

Dexmedetomidine:

↑ patient interaction

↔ time at target sedation

↔ Duration ventilation

↔ ICU / Hosp LOS // Death

Fever Control200 pts with septic shock requiring

vasopressors

External cooling (36.5 to 37°C) vs not

Cooling was associated with

Early ↓ vasopressors

↑ ICU shock reversal

↓ 14 day mortality

EDEN• 1000 pts early ALI

• Initial trophic EN vs full EN

Trophic feeding Δ -900 kcal/day

↔ Ventilator free days

↔ 60 day mortality

↔ Infectious complications

Full EN: ↑ GI complications

LIFENOX8,307 acutely ill medical patients with

graduated compression stockings

subcutaneous enoxaparin (40 mg

daily) vs. placebo

↔D30 death (4.9% vs 4.8%)

↔Bleeding (0.4% versus 0.3%)

BALTI-2

• 326 pts with ARDS

• salbutamol (15 μg/kg/h) vs. placebo

• Trial stopped early for safety

• ↑Mortality 34% vs 23%

Risk ratio 1.47

Good Luck.

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FFICM16