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FFICM Preparation Day London February 26th 2014

Rob Mac Sweeney

Critical Care Literature

• >300 Journals• Major Studies• Major Guidelines• Relevant Review Articles• Commentaries• Editorials• Supplements

• Free Material

Conflict of Interest Statement

•Not for profit site•Completely independent• I make no money from it

Hot Topics

• 2013 • 2012

• Major Research• Major Guidelines• Resources

Major Research Studies2013

TTM Study

• Randomized, parallel group study• 950 unconscious adults• 33°C (n=473) with 36°C (n=466)• No difference in• All cause mortality

• 33°C (50%) with 36°C (48%)• poor neurological function

• 33°C (54%) with 36°C (52%)

Kim Study

• Randomized, parallel group study• Prehospital cooling vs. standard care• 1,359 OOHCA patients• Cooling effective (reduced temp)• No difference• Survival to hospital discharge

• VF 63% vs 64% • nonVF 19% vs 16%

• Good neurological recovery• VF 57% vs 62% • nonVF 14% vs 13%

CATIS Study

• Randomized, parallel group study• 4,071 patients • Within 48 hrs ischemic stroke • nonthrombolysed and ↑SBP• Hypertension therapy vs no BP Rx• BP control effective• No difference• death and major disability

• 14 days / hospital discharge• 3 months

INTERACT2

• Randomized, controlled parallel group study• 2,839 pts with early spontaneous

intracerebral haemorrhage & ↑SBP• Compared SBP <140 mmHg vs <180• Aggressive BP control associated with• Trend for less adverse events (p=0.06)• Lower modified Rankin scores

• No difference in mortality

CRISTAL Study

• Randomized, stratified, open label, assessment blinded study• Any crystalloid vs any colloid• All fluid interventions other than fluid

maintenance in ICU• No difference• 28 day mortality (Col: 27% vs Cry: 25.4%)

• Colloids associated with improved• 90 day mortality• Days alive without mechanical ventilation• Days alive without vasopressor support

TracMan

• Randomized, parallel group study• 909 intubated patients • Respiratory failure• < 4 days• Predicted to need MV for further 7 days

• Tracheostomy timing• Early (≤ 4 days) vs late (after 10 days)• No difference in • Mortality / ICU LOS / Complications

• Only 45% late group received trache

β Blockade in Septic Shock

• Randomised, open-label, phase 2 study• 154 septic patients• Tachycardic & requiring high dose NA• Esmolol (HR 80 – 94) vs standard Rx• Esmolol effective at HR control• Esmolol associated with improved:• HR / SVI / LVSWI / lactate• NA requirement• Fluid requirement• 28 day mortality (49% vs 80%)

STATIN-VAP Study

• Randomized, controlled, blinded, parallel-group, multi-center trial• 300 patients with suspected VAP • Simvastatin 60 mg vs placebo• Study stopped early for futility• No difference in • 28 mortality• Duration mechanical ventilation• Δ SOFA

• Increased mortality in statin naïve• 21.5% vs 13.8%; p=0.054

VSE Study

• Randomized, double-blind, placebo-controlled, parallel-group trial• 268 pts with in-hospital cardiac arrest• Adrenaline/Vasopressin/

Methylprednisolone acutely & hydrocortisone later• VSE associated with improved

• ROSC (84% vs 66%)• Survival with good neurological recovery

(14% vs 5%)• Survival with good neurological recovery in

those with post resuscitation shock (21% vs 8%)

PROSEVA

• Randomised, multi-centre, parallel group study• 466 patients with severe ARDS• Prone position vs supine position• Prone position was associated with• Improved mortality

• 28 day: 16% vs 33%• 90 day: 23.6% vs 41.0

• Less cardiac arrests• No difference in complications

VILLANEAU

• Randomised, parallel group study• 921 pts with severe upper GI bleeding• Compared restrictive (Hb <7g/dL) vs

liberal transfusion strategy (Hb<9g/dL)• Restrictive strategy associated with• Reduced number of pts receiving

transfusion (15% vs 51%)• Increased probability survival (HR 0.55)• Less rebleeding (10% vs 16%)• Less adverse events (40% vs 48%)

REDOXS

• Randomised, blinded, 2x2 factorial study• 1,223 critically ill pts with MOF• Glutamine, antioxidants & placebo• Glutamine associated with harm

• Increased mortality• Trend at 28 days (34% vs 27%; p=0.05)• Increased at 90 days (44% vs 37%; p=0.02)

• Antioxidants ineffective• Mortality• Other endoints

OSCILLATE

• Multi-centre, randomised, controlled, parallel group, trial• 548 pts with new-onset, moderate-

to-severe ARDS• Trial terminated early• Excess mortality 47% vs 35%; RR 1.33• HFOV associated with• Higher sedation requirements• More neuromuscular blockade• Higher vasopressor support

OSCAR

• Multi-centre, randomised, controlled, parallel group, trial• 795 pts moderate-to-severe ARDS• No difference in• Mortality 41% vs 41%• Duration antimicrobial agents• Duration pharmacological vasoactive

support• ICU LOS• Hospital LOS

CRICS

• Randomized, noninferiority, open-label, multicenter study• 452 pts receiving

• Mechanical ventilation > 2 days• Enteral nutrition within 36 hours of MV

• Monitoring gastric volume or not• No difference in

• VAP (15.8% vs 16.7%)• Other ICU-acquired infections• Duration MV / ICU LOS / Hospital LOS

• Higher proportion reached calorific goal (OR 1.77)

SUNSET-ICU

• Single-centre, block, randomised trial• Resident nighttime intensivist vs non-

resident nighttime intensivist• Resident nighttime intensivist not

associated with improvements in• ICU LOS• Mortality• Other endpoints

Early Parenteral Nutrition

• Randomised, single-blinded, parallel group study• Early PN in patients with relative

contraindications to early EN versus early starvation• 1,372 patients• Standard group: 40 % unfed• Nutritional delivery difference until D7• No difference in • 60 day mortality • LOS – ICU or Hospital

• PN - Shorter duration ventilation

Prasad – Medical Reversal

• Retrospective observational study• Looked at 10 years of NEJM

publications• Medical reversals – current practice

inferior to a prior standard• 146/363 studies• 40%

Neurological

• Shehabi. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study (SPICE study). Intensive Care Med 2013;39(5):910-918• Page. Effect of intravenous haloperidol on the duration of delirium

and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respiratory Medicine 2013;epublished August 21st• Mourvillier. Induced Hypothermia in Severe Bacterial Meningitis: A

Randomized Clinical Trial. JAMA 2013;epublished October 8th

Circulatory

• Mylotte. Primary Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction, Resuscitated Cardiac Arrest, and Cardiogenic Shock. The Role of Primary Multivessel Revascularization. J Am Coll Cardiol Intv 2013;6(2):115-125• Mahjoub. Evaluation of pulse pressure variation validity criteria in

critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth 2013;epublished December 29th

Respiratory

• Goodacre. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial. Lancet Respiratory Medicine 2013;epublished May 17th• Hernandez. The effects of increasing effective airway diameter on weaning from

mechanical ventilation in tracheostomized patients: a randomized controlled trial. Intensive Care Med 2013;epublished March 8th• Figueroa-Casas. Accuracy of the chest radiograph to identify bilateral pulmonary

infiltrates consistent with the diagnosis of acute respiratory distress syndrome using computed tomography as reference standard. J Crit Care 2013; epublished April 5th• Thille. Comparison of the Berlin Definition for Acute Respiratory Distress Syndrome

with Autopsy. Am J Respir Crit Care Med 2013;epublished January 31st

Infection Control

• Harris. Universal Glove and Gown Use and Acquisition of Antibiotic-Resistant Bacteria in the ICU: A Randomized Trial. JAMA 2013;epublished October 4th• Huang. Targeted versus Universal Decolonization to Prevent ICU Infection.

N Eng J Med 2013;epublished May 29th• Climo. Effect of Daily Chlorhexidine Bathing on Hospital-Acquired

Infection. N Engl J Med 2013;368:533-542

Sepsis

• Bernard. Evaluating the Efficacy and Safety of Two Doses of the Polyclonal Anti-Tumor Necrosis Factor-[alpha] Fragment Antibody AZD9773 in Adult Patients With Severe Sepsis and/or Septic Shock: Randomized, Double-Blind, Placebo-Controlled Phase IIb Study. Crit Care Med 2013;epublished December 11th

• Opal. Effect of Eritoran, an Antagonist of MD2-TLR4, on Mortality in Patients With Severe Sepsis: The ACCESS Randomized Trial. JAMA 2013;309(11):1154

• Annane. Recombinant Human Activated Protein C for Adults with Septic Shock: a Randomized Controlled Trial (APROCCHSS Trial). Am J Respir Crit Care Med 2013; epublished March 22nd

• Guntupalli. A Phase 2 Randomized, Double-Blind, Placebo–Controlled Study of the Safety and Efficacy of Talactoferrin in Patients With Severe Sepsis. Critical Care Medicine 2013;41(3):706-716

• Kruger. A Multicentre Randomised Trial of Atorvastatin Therapy in Intensive Care Patients with Severe Sepsis. Am J Respir Crit Care Med 2013;epublished ahead of print

Miscellaneous

• Marik. Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense. Critical Care Medicine 2013;41(7):1774-1781• Schnell. Renal Perfusion Assessment by Renal Doppler During Fluid

Challenge in Sepsis. Crit Care Med 2013;41(5):1214-1220• Cooper. Albumin Resuscitation for Traumatic Brain Injury: Is Intracranial

Hypertension the Cause of Increased Mortality? J Neurotrauma 2013; epublished March 21st• Casaer. Role of Disease and Macronutrient Dose in the Randomized

Controlled EPaNIC Trial. Am J Respir Crit Care Med 2013;187:247-255

Podcasts

Major Guidelines2013

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 Studies2012

EN vs EN & PN

• Two-centre, randomized controlled, parallel group study• 305 critically ill patients • Day 3 & received <60% calorific goal• EN plus PN to achieve 100% calorific

target vs EN alone• EN plus PN was associated with• Greater calorific intake: 28 vs 20

kcal/kg• Less infection: 27% vs 38%

Best TRIP

• Randomised, controlled trial• 324 pts with severe traumatic brain

injury• ICP guided vs clinical and imaging

guided management• No difference in• Composite of functional & cognitive

measures• 6 month mortality (ICP 39% vs C&I: 41%)• Length of stay

• Imaging clinical group received more days of brain specific therapies

CARRESS

• Randomised, parallel group study• 188 pts with acute decompensated

heart failure• Stepped pharmacological therapy vs

ultrafiltration• Greater creatinine rise with UF• +20.3±61.9 μmol/l vs −3.5±46.9 μmol

• No difference in weight loss• - 5.5±5.1 kg vs - 5.7±3.9 kg

• More complications with UF• 72% vs. 57%

SLEAP Study

• Randomised, controlled, parallel group study• 423 mechanically ventilated pts• Protocolised sedation vs protocolised

sedation plus daily sedation break• No difference in• Time to extubation• ICU LOS / Hospital LOS• Delirium / Unintended extubations

• Daily break in sedation associated with• more sedation / nursing interventions

CHEST study

• Randomised, controlled, parallel group study• 7000 ICU pts• Fluid resuscitation with 6% HES

130/0.4 (Voluven) or 0.9% saline• No differences in• Mortality (HES 18% vs 17%)• LOS – ICU / Hospital

• HES associated with increased• RRT (7% vs 5.8%; RR 1.21)• Pruritus / Rash / Hepatic failure

6S Study

• Randomised, controlled, multicentre, parallel group study• 804 ICU pts with severe sepsis• Compared fluid resuscitation • 130/0.4 hydroxyethyl starch (tetraspan)

vs Ringer's acetate

• HES associated with• Increased 90 day mortality (51% vs 43%)• Increased RRT requirement (22% vs

16%)• Trend for increased bleeding (10% vs

6%, p=0.09)

IABP-II Study

• Randomised, open-label, multicentre, parallel group study• 600 pts with acute MI & cardiogenic

shock• IABP vs no IABP• No difference in• 30 day mortality (IABP 40% vs 41%)• Time to haemodynamic stabilisation• ICU LOS• Catecholamine therapy• Bleeding or other comlications

PROWESS SHOCK Study

• Randomised, controlled, multicentre, parallel group study• 1,697 patients with septic shock• No difference in• 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

• Randomised, placebo-controlled, multicentre, parallel group study• 1,204 pts within 4 days of

aneurysmal SAH• MgSO4 (64 mmol/day) ve placebo• No difference in• Functional outcome• 90 day mortality (MgSO4 26% vs 25%)

PRODEX / MIDEX

• Two phase 3, non-inferiority RCTs• MIDEX (n=500)• Dexmedetomidine associated with

• Decreased duration of ventilation• Increased patient interaction• Increased hypotension & bradycardia

• No difference in• time at target sedation• ICU LOS / Hospital LOS / mortality

PRODEX / MIDEX

• PRODEX (n=437)• Dexmedetomidine associated with • Increased patient interaction

• No difference in• time at target sedation• Duration mechanical ventilation• ICU LOS / Hospital LOS / mortality

Fever Control in Sepsis

• Randomised, multi-centre, parallel group trial• 200 pts with septic shock requiring

vasopressors• External cooling (36.5 to 37°C) vs not• Cooling effective (36.8 C vs 38.4)• Cooling was associated with• Early 50% reduction in vasopressor

requirement (54% vs. 20%)• Greater ICU shock reversal (86 vs. 73%)• Improved 14 day mortality (19 vs. 34%)

EDEN

• Randomized, open-label, multi-centre, parallel group study• 1000 patients ≤ 48 hrs of ALI & MV• Initial trophic EN vs initial full EN• Trophic feeding Δ -900 kcal/day• No difference in

• Ventilator free days• 60 day mortality• Infectious complications

• Full EN associated with• More vomiting / greater residual gastric

volumes / prokinetic use / constipation

LIFENOX

• Randomised, placebo-controlled, parallel group study• 8,307 acutely ill medical patients with

graduated compression stockings• subcutaneous enoxaparin (40 mg

daily) vs. placebo• No difference• 30 day mortality (4.9% versus 4.8%)• Bleeding (0.4% versus 0.3%)

BALTI-2

• Randomised, placebo-controlled, parallel group study• 326 pts with ARDS• salbutamol (15 μg/kg/h) vs. placebo• Trial stopped early for safety• Increased mortality 34% vs 23%• Risk ratio 1.47

Major Guidelines2012

KDIGO AKI Guideline

ESICM Colloids Guideline

STEMI Guideline

STEMI Guideline

Heart Failure Guideline

Other Resources

Other Resources

• Podcasts• Vodcasts• Journals• Websites• Societies• Guidelines• Practice Questions

Tips

• ICS guidelines• Brainstem testing• Staffing levels

• NICE guidelines• AKI

• AAGBI• NAP • Airway• Tracheostomy care

Good Luck.

rob@criticalcarereviews.com