Hot Topics.

FFICM Preparation Day London February 23rd 2015

Rob Mac Sweeney

Hot Topics

•2015

•2014

•2013

•2012

•Major Research

•Major Guidelines

Major Research Studies

2015

Amato Study● Post hoc review of 9 RCTs

● Multilevel Mediation Analysis

● Functional Lung Size

● ΔP = (Pplt – PEEP) = (Vt /CRS

)

● Vt / Pplat / PEEP →ΔP

● ΔP 7 cmH20 = ↑41% mortality

● Requires validation

PROPPR● Pragmatic multicentre RCT

● 680 severely ill trauma patients

● 1:1:1 with 1:1:2 FFP / Plt / RC

● ↔ mortality:

● Day 1

● Day 30

● Reduced exsanguination deaths

● 1:1:2 group “caught up”

Chlorhexidine Bathing● Pragmatic, Cluster Randomized

Crossover study

● 9340 patients

● Once daily 2% chlorhexidine

● 2 x 10 week periods each

● ↔ in infections

● 55 vs 60

● 2.86 vs 2.90 / 1000 pt days

Major Guidelines

2015

SSAI - Fluid Resuscitation

Ascites Club

Major Research Studies

2014

ALBIOS● Multicentre Open Label RCT

● 1795 patients with sepsis / shock

● 20% albumin + crystal vs crystal

● Target serum albumin > 30g/l

● ↔ 28 day mortality

● Albumin: 31.8% vs 32%

● ↔90 day mortality

● Albumin: 41.1% vs 43.6%

ARISE ● Australian / NZ RCT

● EGDT vs Usual Care

● Rivers algorithm

● 1600 patients with septic shock

● ↔90 mortality

● EGDT 18.6% vs 18.8%

● EGDT - more fluids,

vasopressors, RC, dobutamine

ProCESS● American multicentre RCT

● Testing Rivers EGDT protocol

● EDGT vs Standard vs Usual care

● 1341 patients with septic shock

● ↔ day 60 mortality

● 21% vs 18.2% vs 18.9%

● ↔ day 90 or 1 year mortality

CALORIES ● Pragmatic, open label RCT

● Enteral vs Parenteral nutrition

● Could be fed by either route

● 2400 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 CPR

● USA / European - OOHCA

● 4753 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 RCT

● Mechanical CPR & defibrillation

● 2589 OOHCA patients

● ↔ 4 hr survival: 23.6% vs 23.7%

● ↔ CPC 1-2 survival

● At ICU / Hospital discharge

● At 1 or 6 month

HARP-2 ● Multicentre, UK/Ireland RCT

● Simvastatin vs Placebo

● 540 patients with ARDS

● ↔ Ventilator-free days

● ↔ Non-pulmonary organ

failure -free days

● ↔28 day mortality

METAPLUS ● European multi-centre RCT

● 301 pts expected ventilated >3/7

● Immune enhancing nutrients

● High protein diet both groups

● ↔new infections (53% vs 52%)

● ↑ 6/12 mortality with IMN

● 54% vs 35%

PEITHO ● European Multi-centre RCT

● 1,006 pts intermediate risk PE

● Tenecteplase & 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

SEPSISPAM● Multi-centre open label RCT

● 776 pts with septic shock

● MAP 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

TRISS● European multi-centre RCT

● 1005 pts septic shock & anaemia

● Transfuse Hb <9 g/dl vs <7 g/dl

● Less blood given (median 4 vs 1)

● ↔D90 mortality (45% vs 43%)

● ↔ischaemia / adverse events

VITdAL-ICU● Austrian single centre RCT

● 492 white ICU pts Vit D deficient

● Vit D vs Placebo

● ↔Hosp LOS 20 vs 19 days

● ↔ Hosp / 6/12 mortality

● Severely deficient subgroup

● ↓Hosp mortality 28% vs 46%

● ↔ Hosp / 6/12 mo

Major Guidelines

2014

ESICM -Neuroprognostication

ESICM - Shock

ESC – Cardiac Tamponade

ESC – Pulmonary Embolism

ESC – Revascularization

JSICM – Sepsis

SSAI - ARDS Ventilation

ADQI – AKI Biomarkers

NICE – Acute Heart Failure

UK - CPR Guidance

CCCS - Ebola

Major Research Studies

2013

TTM Study● Multi-centre RCT

● 950 OOHCA Patients

● 33°C vs 36°C

● ↔All cause mortality

● 50% vs 48%

● ↔Poor neuro function

● 54% vs 52%

Kim Study● Prehospital 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 Study● 4,071 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

INTERACT2● Early 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 RCT

● Any colloid vs any crystalloid

● 2857 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

TracMan

● 909 intubated patients

● Tracheostomy timing

● ≤ 4 days vs > 10 days

● ↔Mortality / ICU LOS

● ↔Complications

● Only 45% late group received trache

β Blockade in Septic Shock

● 154 septic pts with ↑HR & ↑dose NA

● Esmolol vs standard Rx

● Esmolol

● ↓ HR / lactate / Norad / Fluids

● ↑ SVI / LVSWI

● ↓ D28 mortality (49% vs 80%)

STATIN-VAP● 300 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 pts● Adrenaline/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)

PROSEVA

● 466 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

REDOXS● 1,223 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

OSCAR● 795 pts with moderate-to-severe

ARDS

● ↔Mortality 41% vs 41%

● ↔Duration antimicrobials

● ↔Duration pharmacological

vasoactive support

● ↔ LOS ICU or Hospital

CRICS

● 452 ventilated pts

● Not monitoring gastric volume

•↔VAP (15.8% vs 16.7%)

•↔ ICU-acquired infections

•↔Duration MV / ICU

or Hospital LOS

• ↑calorific goal (OR 1.77)

SUNSET-ICU

● Single-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

Reversal● Retrospective observational

● Looked at 10 years of NEJM

publications

● Medical reversals – current practice

inferior to a prior standard

● 146/363 studies

● 40%

Major Guidelines

2013

Surviving Sepsis Campaign

Pain, Analgesia & Delirium

Trauma Haemorrhage

Difficult Airway

Difficult Airway

Difficult Airway

Acute Pancreatitis

Red Cell Transfusion

Red Cell Transfusion

Red Cell Transfusion

Canadian Nutrition Guideline

Major Research Studies

2012

EN vs EN & PN

● 305 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 TRIP● 324 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● 188 pts with acute decompensated

heart failure

● Stepped pharmacological therapy vs

ultrafiltration

● UF: ↑complications

↑creatinine

● +20.3 vs −3.5 μmol

● ↔weight loss

● - 5.5±5.1 vs - 5.7±3.9 kg

SLEAP Study● 423 pts

● Protocolised sedation vs PS plus daily

sedation break

● ↔ Time to extubation

● ↔ ICU LOS / Hospital LOS

● ↔ Delirium / Unintended

extubations

● PS & DSB: ↑sedation / nursing

CHEST study● 7000 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 Study

● 804 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 Study

● 600 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 Study

● 1,697 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-2

● 1,204 pts within 4 days of

aneurysmal SAH

● MgSO4 (64 mmol/day) vs placebo

● ↔Functional outcome

● ↔90 day mortality

● MgSO4 26% vs 25%

PRODEX / MIDEX● MIDEX (n=500)

● Dexmedetomidine v Midaz

● Dexmedetomidine:

● ↓duration ventilation

● ↑patient interaction

● ↑hypotension / bradycardia

● ↔ time at target sedation

● ↔ ICU / Hosp LOS / death

PRODEX / MIDEX

● PRODEX (n=437)

● Dexmedetomidine v Propofol

● Dexmedetomidine:

● ↑patient interaction

● ↔time at target sedation

● ↔Duration ventilation

● ↔ICU / Hosp LOS // Death

Fever Control● 200 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

LIFENOX

● 8,307 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

Major Guidelines

2012

KDIGO AKI Guideline

ESICM Colloids Guideline

STEMI Guideline

STEMI Guideline

Heart Failure Guideline

Good Luck.

rob@criticalcarereviews.com@critcarereviews