Hot Topics in ICM - PINCER Course 25th sept 2015

Academic Department of Critical Care
Queen Alexandra Hospital Portsmouth
Hot Topics in ICM
Steve Mathieu
@stevemathieu75 @WessexICS
Consultant in Intensive Care Medicine
Queen Alexandra Hospital, Portsmouth
15th September 2015 
 
& some question spotting…

Examiners Report 
April/May 2014
http://www.ficm.ac.uk/sites/default/files/document-files/EXM-FFICM-Summary-ChairmanReport-April2014_0.pdf

Examiners Report 
Nov 2014
http://www.ficm.ac.uk/sites/default/files/Critical%20Eye%207%20-%20Winter%202015_0.pdf
‘some candidates appeared to consider that
they should concentrate only on areas within
their own experience rather than the breadth
of the syllabus’

Examiners Report 
April 2015
http://www.ficm.ac.uk/sites/default/files/Critical%20Eye%208%20-%20Summer%202015%20FINAL%20WEBSITE2.pdf
“A doctor in training who is familiar with the syllabus and has done
the necessary bookwork. They would clinically be at the level of a
registrar who would be able to formulate a plan of care for a
critically ill patient with appropriate consultant backup. Passing the
exam is a requirement of progression to ST7 of the intensive care
medicine training programme and the standard is set to reflect
this”.

Hot Topics/Question spotting
• Examiners report
• Syllabus
• Review articles & key papers – JICS
• Guidelines
• Review FICM & ICS websites
• Critical Eye
• Other resources

Original Articles Reviews Case reports CAT reviews Others
August 2015 Psychological and
neurocognitive
consequences of
critical illness

Weight calculations

Scoring system for
cirrhosis
NIV post
oesophagecotmy.
Safe?
Thyroid storm

NAC
PARAMEDIC study
(mechanical vs
manual CPR)

Damage control
resuscitation
Prevention of VTE

Anatomy of vessels
relevant to central
line placement

NIV

Defining death

Stridor
May 2015 Tracheostomy care

Depression following
critical illness

Consultant cover and
working practice

ICU acquired
weakness

Pharmacokinetic
considerations and
dosing strategies of
antibiotics
Strep toxic shock ProMISe

CRISTAL Colloids vs
crystalloids
Feeding patients
with tracheostomies

Amitryptiline OD

Managing acute
central nervous
system infections in
the UK adult
intensive care unit in
the wake of UK
encephalitis
guidelines
Feb2015 Adult blunt chest
trauma

RRT in Scottish ICUs

Rehab after critical
care
Troponin elevated in
sepsis
DKA Monitoring-based
antibiotic
optimisation

VSE after IHCA
Rehab

Improving quality

GPICS

DoLS + DoLS

Ebola

Tracheostomy

Acute
cardiomyopathy with
amphetamine
poisoning

October 2014 Minimising warm and
cold ischaemic times
liver transplants

DoLS +++

Oral Feed and
Tracheostomy

Prophylactic IVC Filter
ECCO2R in NIV

Limbic encephalitis

Emphysematous
pyelonephritis

Ondine’s Curse
Volume-Outcome
Relationships for MV
Adult Patients

Hyperglycaemic
control on PICU
Evacuation of ICU
due to a Fire

Letter about VAP

Hyperoxaemia in
SAH

Electrical Muscle
Stimulation in ICU
July 2014 Echo in PE

Quality (pressure
ulcers)
DKA

Acute mesenteric
ischaemia
Epidural abscess

JW

GI haemorrhage

Mixed OD

Acromegaly
Statin & VAP

SEPSISPAM

Protective ventilation
in abdominal surgery

Heart rate control in
septic shock
Delirium
April 2014 Tracheostomy

VAP

Improving timeliness
of time-critical
transfers
HIT

Hepatitis B & C

Sedation

Electrical muscle
stimulation in ICU
(CIPN)
HD for dabigatran
associated
coagulopathy

Wernickes

Patient with tetanus
TBI

Hope ICU (delirium)

CSL or HES

TTM
Prone ventilation

Capnography
Jan 2014 COMET-UK (CO
monitoring)

Tracheostomy
Right heart failure

Stabilisation and
transport of critically
ill child
ECG and trauma

Rhabdomyolysis

Pancreatitis

MDMA toxicity

Hyperthyroidism

Pulmonary
haemorrhage and
AKI
TracMan AKI

Organ donation

Surveillance for VAP

PE supplement

Original Articles Reviews Case reports CAT reviews Others
October
2013
Echo NAVA ventilation

Pain

Brainstem testing
Plasma exchange in
HUS

Intralipid in felodipine
toxicity

Tracheostomy
Transfusion strategies
for upper GI bleed

Prone

TXA
Survey on rehab after
critical illness

Echo in UK

Blood transfusion in
ICU

BIS monitoring

Faecal incontinence in
ICU
July 2013 Noise level in ICU
(delirium)
Serious Hazards of
Transfusion (SHOT)

Medical support for
heart failure

PCT

NO

Cardiogenic shock
OTC deficiency

Hyperkalaemia in HIV
patient with ‘PCP’
ICP monitoring

Sedation
Gentamycin &
vancomycin

Ancillary tests in
diagnosis of brainstem
testing

LCP

Scoring systems for
CAP

Atrial Fibrillation in
ICU

Guidelines

The Sepsis Studies

Neuro
http://www.wessexics.com/WICS_Guidelines/
The SAH section
definitely worth a
read for the exam

NCEPOD 2014: Tracheostomy
• Documentation & consent
– Indications, type, inner tube,
reasons for failed extubation/
why no trial of extubation
• Different types of tubes
• Rapidly available difficult airway
trolley
• Training programmes in blocked/
displaced tubes
• Capnography
• Discharge of patients with
tracheostomy
• MDT – physio & SALT
Capnography
Airway equipment
Back up planning
Staffing
Patient transfers
Education/training
Tracheostomy tube
design
Team working

Tracheostomy standards ICS
• Indications for tracheostomy
• Cautions and contraindications
• Consent
• Equipment
• Ultrasound
• Anaesthesia
• Staffing
• Types of tracheostomy tubes
• Inner cannulae
• Complication
– Early
– Late
– Airway emergencies

21
HFNC non inferior to facemask and NIV in ALI

ABLE Multicentre UK RBC transfusion (7d vs. 15-25d)
NOAC
Transfusion triggers – TRICC, TRISS & Villaneuva, TITRe2
PROPPR: Plasma, Platelets & PRBC’s 1:1:1 vs. 1:1:2
Management of anaemia & RBC transfusion BCSH Guidelines 2012)
Serious Hazards of Transfusion (SHOT) – JICS July 2013

Standards - quality
• Staffing
– Consultant presence
• 24/7 & within 30 minutes
– Consultant: patient 1:8 – 1:15; ICU resident/patient
1:8
– Designated CD
– Ward rounds x2 daily
– Training / FICM / Board Tutors
– Nursing 1:1 (level 3); 1:2 (level 2)
– MDT e.g. physio, pharmacy, dieticians
• Operational
– Large ICUs divided into pods of 8-15 patients
– Admit within 4 hrs of decision to admit
– Avoid non-clinical transfers
– Transfer to ward – clear and formalised
– Out of hours transfers
– Readmission within 48 hours bad
– Assessment of rehab for each patient
• Equipment
– Training
• Data Collection
– ICNARC
– Risk register
Quality Indicators
SMR
Scoring Systems

MCA & DoLS
DoLS
• 3 cases in 2014
MUST READ….

The landmark papers in Critical Care

NAP 4 - 2011
• All NHS hospitals for 1 year ’08-’09
• 184 reports
133 anaesthesia
36 ICU
15 ED
• Inclusion criteria
death, brain damage
emergency surgical airway
unanticipated ICU admission
– Prolongation ICU stay

Summary of NAP 4
25% of major airway events in a hospital occur in ICU or the
ED
46% of ICU events and 53% of ED events occurred out of hours
50% of ICU events were due to tracheostomy related events
50% events in ICU and 27% events in ED resulted in death
61% events in ICU resulted in death or severe neurological
harm

Recommendations
Capnography
Airway equipment
Back up planning
Staffing
Patient transfers
Education/training
Tracheostomy tube
design
Team working

TracMan - 2013
•Early tracheostomy (by d 4) or late
(>10/7)
– 455 patients
– Mortality the same 31%
– LOS the same 13 d
– Complications slightly higher in late group
6% vs. 5%
Young et al. JAMA 2013 May 22;309(20):2121-9

ARDS - Incidence
• 1 yr prospective
observational study; 255
patients
• Incidence 7.2/100,000/
year (? US 75/100,000)
• Despite use of lung
protective ventilation
overall ICU mortality
>40%

OSCAR
• 795 patients with moderate -
severe ARDS (<26.7kPa /
200mmHg)
• CMV vs. HFOV (MV <7 days)
• No difference in
– 30/7 mortality (41%)
– Duration antimicrobial agents (2/3
chest sepsis)
– Vasoactive support duration
– ICU LOS
– Hospital LOS

OSCILLATE
• 548 patients with moderate - severe
ARDS
• HFOV vs low Vt/High PEEP CV (MV <
3d)
• Trial stopped early as harm with HFOV
• HFOV
– Hospital mortality 47% vs 35%
– More sedation
– More NMBA’s
– More vasopressors

PROSEVA
• 466 patients with severe ARDS
• Prone position vs supine position
• Prone position was associated
with
– Improved mortality
• 28 day: 16% vs 33%
• 90 day: 24% vs 41%
– Less cardiac arrests
– No difference in
complications

PROSEVA

HARP 2 - 2014
• 540 patients ARDS; 40 UK ICUs
• ARDSnet +/- statin for 28 days
(80mg od simvastatin)
• Primary outcome
– No difference in ventilator free
days at 28d
• Secondary outcome
– No difference in SOFA, oxygenation
– Elevated CK or ALT/AST > in statin
group

Statins in ARDS
• Multicentre, RCT
• Rosuvastatin vs. placebo in ARDS
• Statin may modulate inflammatory response
• 745 patients (trial stopped early because of
futility)
• Primary outcome:
• 60d mortality: 28.5% vs. 24.9% (statin vs. placebo)
• Ventilator free days: 15.1 vs. 15.1

Statin & VAP
• 300 patients with suspected VAP
(CPIS ≥ 5)
• Simvastatin 60mg vs placebo
– 28d survival
– ICU or hospital mortality
– Duration MV
– Delta SOFA
• Increased mortality in statin naieve

BALTI - 2012
• 162 patients; 46 UK ICU’s
• ARDS & MV
- salbutamol 15mcg/kg/hr or placebo
- Treatment for up to 7 d
• Mortality greater in those given
salbutamol 34% vs 23% at 28d

Steroids in ARDS
• 9 studies (4 RCT’s & 5 cohort)
• 648 patients
• Trend to reduced mortality but
only ss when result pooled
• Trials vary ++
1.Dose
2.Initiation of treatment
3.Course length
4.Not all studies report adverse events

Nitric oxide – just say No
• Potent pulmonary vasodilator which when inhaled =
selective vasodilation in well ventilated lung units
• Improved V/Q mismatch and PVR & PAP
• Also anti-inflammatory effects
• Systematic review of 12 trials with 1200 patients =
improved oxygenation d1, no improvement in
mortality
• ⇧AKI and methaemaglobinaemia
⇧intracranial bleeding in children
Afshari Cochrane review 2007 - adults
Barrington Cochrane review 2010 – children
Afshari – systematic review 2011

Magnesium in asthma
• 1200 patients 2008-2012
• Neb vs. IV Mg vs. placebo
• No role for neb Mg
• Limited role at best for IV
Mg
• Not life threatening
asthma
Intravenous or
nebulised magnesium
sulphate versus
standard therapy for
severe acute asthma
(3Mg trial): a double-
blind, randomised
controlled trial
Goodacre et al Lancet 2013 Vol 1 (4) 293-300

VAP
What is VAP?
What are the common organisms (early
vs. late?
Scoring systems e.g. CPIS, HELICS
What antibiotics would you use?
How can you reduce incidence
Open Access!
#FOAMcc

50
HFNC non inferior to facemask and NIV in ALI

FLORALI
• 12 French ICU’s; 310 patients
• ‘ALI’
• NRB vs HFNC vs NIV
• Primary outcome: Proportion of patients who required
endotracheal intubation within 28 days after
randomisation:
• High-Flow oxygen: 40 patients (38%)
• Non-invasive ventilation: 55 patients (50%)
• Standard oxygen: 44 patients (47%)
• p = 0.18

PREOXYFLOW
• 6 French ICUs. 119 patients
• Acute hypoxaemia
• Primary outcome: Lowest SpO2 during the
endotracheal intubation (ETI) procedure
• ETI = the beginning of laryngoscopy to
patient connection to the mechanical
ventilator
• HFNC 91.5 [80-96] vs HFFM 89.5% [81–95] p =
0.44.
• HFNC without discontinuation during an
apnoeic period, was not any more effective
than using a high FiO2 facemask at 15 l/min
for preventing desaturation during RSI

CO Monitoring – COMET-UK
• Survey to all UK ICUs
• Respondents
– Majority used CO monitoring
• Oesophageal doppler 57%
• LiDCO 43%
• PiCCO 42%
How does doppler work?
Thermodilution?
Pulse contour analysis ?

OPTIMISE
• RCT, multicentre, 17 UK ICUs
• 734 patients
• > 50y undergoing GI surgery with one or more ‘high risk’ risk factors
• Algorithm-directed care dictating colloid and dopexamine
administration using vs. clinician directed care without use of CO
monitoring
• Primary outcome: composite of 30d mortality and mod/major
complications
– Intervention: 36.6%
– Control arm: 43.4%
• No SS difference in secondary outcomes
– POMS, infectious complications, critical care free days at 30d, mortality
at 30d and 180d, hospital LOS

IVOIRE Study
• Randomised, open study
• 18 ICU’s in France, Belgium and
Netherlands 2005-2010
• 140 pts with septic shock & AKI
• HVHF 70mls/kg/hr v 35mls/kg/hr
• Slow recruitment
• No difference in mortality = 40%
28/7
• HVHF not recommended

TTM
• 950 unconscious adults; 36 ICU’s
• 33°C (n=473) with 36°C (n=466)
– All cause mortality
33°C (50%) with 36°C (48%)
– poor neurological function
at 180 days
33°C (54%) with 36°C (52%)

Cognitive function post TTM
• 652 cardiac arrest survivors from TTM
• Survival until 180 days 52%
- invited to follow up
- about half had psychometric testing
- compared with a control group
(STEMI but no cardiac arrest)
• About 50% had cognitive impairment
• 33 vs. 36 vs. control group similar
• Attention & mental speed more affected in
cardiac arrest patients
• Memory & executive functioning similar

Pre-hospital hypothermia
• Prehospital cooling vs. standard care
• 2L of cold normal saline once ROSC
• 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%

IABP – SHOCK II
• 600 patients with cardiogenic shock
secondary to AMI
• IABP vs no IABP
• All received early revascularisation
and best medical therapy
• No difference
– 30/7 mortality (40%)
– ICU LOS, catecholamine, bleeding
• Lancet 2013 Sept – 12/12 results = no
difference in mortality or reinfarction
rate

VSE in cardiac arrest
• 268 patients in hospital cardiac arrest
• Vasopressin(20IU/CPR cycle) +
epinephrine (1mg/CPR cycle) +
methylprednisilone (40mg) vs placebo
+ epinephrine (1mg/CPR cycle)
• VSE group
– ROSC at 20 mins higher 84% vs 66%
– Improved survival to hospital discharge with
CPC 1 or 2
– Improved haemodynamics & cvSpO2
– Less organ dysfunction
• and

Therapeutic Hypothermia after OOH CA
in Children
In children suffering an out-of-hospital cardiac arrest, does hypothermia (33)
compared to normothermia increase survival with a good neurobehavioural
outcome?
38 sites in US & Canada; 260 patients
There was no statistically significant difference in survival to 12 months with
good neurobehavioural outcome (age-corrected standard score of 70 or higher on
he Vineland Adaptive Behaviour Scale 2nd ed. [VABS-II])

Therapeutic Hypothermia in Deceased Organ
Donors and Kidney-Graft Function
• 394 donors with BSD
• Mild hypothermia (34-35) vs
normothermia
• Primary outcome: Delayed graft function
(the recipient's requirement for dialysis
during the 1st week post-transplantation)
- significantly lower in hypothermia group
• 28.2% vs 39.2%, P=0.008

Monitor: Protocolised fluid therapy in
brain-dead donors
• US
• BSD 508
• Protocolised LiDCO vs routine
• Primary outcome: Number of organs transplanted per donor – no
difference

CHEER
• Refractory cardiac arrest treated
with mechanical CPR, hypothermia,
ECMO and early reperfusion
• 26 patients (11 OHCA; 15 IHCA)
• Primary outcome
– Survival with good neurological recovery (CPC 1-2) 14/26
(54%)
• Secondary outcomes
– ROSC achieved in 25/26 (92%) of patients
– Survival to hospital discharge 14/26 (54%)

The oxygenator in veno-venous ECMO

Study type Year
pub
N
(ECMO
)
N
(non
ECMO)
%
H1N1
ECMO
mortality
Non-
ECMO
mortality
p
RCT 2009 90 90 0 37% 50% 0.07
RCT 1994 21 19 0 67% 58% 0.8
RCT 1979 48 42 0 90% 92% 0.84
Cohort 2006 32 118 0 47% 29% 0.06
Cohort 2000 62 183 0 45% 39% NS
Cohort 1997 49 73 0 45% 11% <0.001
Case
series
2009 68 133 100% 23% 13% 0.06
Case
series
2011 69 11 100% 27.5% ?52% ***

ECMO for H1N1
• 2009-2010
• 80 patients referred for
ECMO
• 69 received ECMO
• 22 of these died (27.5%)
• Matching cohort = 52%
• For patients with H1N1
related ARDS, mortality
reduced with ECMO

• Meta-analysis
• 16 trials inc PEITHO, MAPPETT,
MOPETT, TOPCOT
• Thrombolysis + anticoagulation
vs. anticoagulation alone
• All cause mortality less in
thrombolysis group but major
bleeding & ICH higher

SEPSIS

ARISE
• Randomised, controlled,
multicentre,
• 51 hospitals 1,600 patients with
septic shock
• EGDT vs. Usual Care
• No difference in:
– All cause mortality at 90d (18%)
– ICU & Hospital LOS

ProCESS
• RCT 31 ICUs in US
• 03/2008 – 05/2013
• 1351 patients with septic shock
• 3 groups
– EGDT
– Protocol based standard therapy
– Usual care
– No difference in 60 d mortality between
groups

ProMISe
• RCT 56 ICUs in UK
• 02/2011 – 07/2014
• 1260 patients with septic shock
• EGDT vs Usual care
– All cause mortality at 90 days in EGDT
group vs. usual care group
– 29.5% vs. 29.2% p=0.9

Ferrer: Empiric antibiotics in sepsis
• Retrospective observational cohort study
• 165 ICUs – Europe, US & S America
• Jan 2005- Feb 2010
• 18,000 patients with septic shock
• Delay in antibiotics administration over first 6 hours after
identification of SS or septic shock -> increased mortality
• < 1 hr 24.6%; 1-2h 25.9% > 6h 33%

SEPSISPAM
• RCT, multicentre, 29 French ICUs
• March 2010 – Dec 2011
• Septic shock
• Target MAP 80-85 vs. 65-70
– 28 day mortality (high MAP 36.6% vs. 34%)
• New AF 6.7% in higher MAP group vs. 2.8% P=0.02
• In chronic hypertension group, worsening creatinine and need for RRT
was lower in higher MAP group

PROWESS SHOCK
• Randomised, controlled,
multicentre, parallel group study
• 1,697 patients with septic shock
– 28 day mortality (APC 26.4% vs
24.2%)
– 90 day mortality (34.1% vs 32.7%)
• No subgroup effect seen in protein C
deficient group
• Serious bleeding n = 10 APC vs 8
placebo

B blockers in septic shock
• Open label, single unit
• Septic shock + HR ≥ 95 + NADR
• 77 patients – esmolol infusion (HR
80-94) vs 77 patients standard
treatment
• Esmolol group
– 28d Mortality 50% vs 81% in placebo
– Improved SV index, LVSWI, lactate
– Less NADR requirement
– Less fluid requirement

Esmolol in refractory VF
• Single centre, non randomised
• 25 patients with refractory (>3 defib
attempts) VF or pulseless VT
• Esmolol vs. placebo
• Primary outcome
– Survival with good neurological recovery
– 50% esmolol vs 11% control group
– No difference in rates of ROSC or survival
to hospital discharge

Steroids in Sepsis

The evidence…..let’s give it
8 trials published before ’89
- No mortality benefit (some worse)
- Decreased time for shock resolution
- More secondary infections
- Higher doses and for shorter periods
19 ICU’s 300 patients
- 50mg hydrocortisone + fludrocorisone vs. placebo by 8hrs of
onset of septic shock.
- ‘Non responders’ (adrenal suppression) better ICU (53% vs.
63%) and hospital mortality (61% vs. 72%).
- Increase secondary bacterial infections
- NNT = 7
(Annane JAMA 2002)

The evidence…..perhaps don’t give
CORTICUS
- 52 ICU’s, 499 patients
- 50mg hydrocortisone QDS vs. placebo 6/7
- 28/7 mortality no different between groups and subset of non-
responders
Quicker shock resolution, catecholamine sparing, more secondary
infections
Sprung et al. NEJM 2008: 358; 111-24
- Etomidate used in 1/5th of patients
- Only 35% power to detect a 20% mortality reduction
- High variability between laboratories in cortisol assays

Hang on….
Post hoc analysis of patients in VASST
Review of patients with noradrenaline (293) and steroids and vasopressin (295)
and steroids
28 day mortality difference 44.7% versus 35.9% (p=0.03)
? Increased responsiveness to catecholamines
? Increased vasopressin levels
? Decreased inflammation
Russell J, et al, Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock,
Crit Care Med 2009 Vol. 37, 811-8
VANISH – second arm includes steroids. Eagerly await results

VASST
- RCT 778 pts with septic shock
- Noradrenaline vs. Norad & Vaso (0.03 units/min)
- No mortality benefit
- Higher doses associated with ischaemia
“Possible use if other vasopressors failed”
Less severe shock associated with reduced mortality when vasopressin
used
Russell et al. NEJM 2008: 358: 877-87

VANISH
Vasopressin & corticosteroids in
Septic Shock. A Pilot Study – Gordon
A, 2014
Hydrocortisone
- vasopressin sparing
- reduced duration vasopressin
- reduced dose vasopressin
- no effect on vasopressin levels

ABLE
• RCT 64 ICUs in Canada & Europe
• 2510 patients administered RBC
transfusion up to seven days post ICU-
admission & anticipated length of MV of at
least 48 hours
• "fresh" RBC's (stored for 8 days or less)
compared with standard issue RBCs (stored
2-42 days)
– 90 day mortality
– 448 patients (37%) vs. 430 patients
(35%) (Absolute Risk Difference 1.7%;
95% CI -2.1-5.5)

TITRe2
• RCT 17 cardiac ICUs in UK
• In adults undergoing cardiac surgery,
does a restrictive transfusion
strategy (Hb > 75 g/l) compared to a
liberal transfusion strategy (Hb > 90
g/l) lead to fewer infections and
ischaemic events within 3 months?
• No difference

TRISS
• 32 general ICUs in Scandinavia
• 998 patients with septic shock & Hb <9
• Transfusion threshold <7 vs. <9
• Excluded patients with ACS
– No difference in death at 90 days
• Secondary outcomes: No difference in
• Vasoactive drugs
• Ventilation
• RRT
• % of days alive & out of hospital
• Ischaemic events

Acute UGI Bleed
• 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%)

PROPPR
• RCT in 12 N. American Level 1 trauma centres
• 680 patients
• Transfusion of plasma:plts:PRBCs
• 1:1:1 vs. 1:1:2
- 24 hour and 30d mortality no different
• Secondary outcomes: No difference
Time of haemostasis; Any of 23 pre-defined
complications; Hospital, ventilator & ICU free days
• Post- hoc analysis:
- Death by exasanguination in 1st 24 hrs much
less in 1:1:1 group

PROPPR

TXA
CRASH - 2 Lancet 2010
• tranexamic acid in reducing transfusion requirements and death
from significant haemorrhage following injury
• 20,000 patients
• Risk of haemorrhage reduced by 0.8%
• No reduction in transfusion usage
• Only 50% received blood and average only 3 (? ‘significant
haemorrhage’)
CRASH - 2 subanalysis Lancet 2011
• Mortality directly related to haemorrhage
Tranexamic acid only effective if within first 3 hours. Beyond
this time mortality increases

TXA
CRASH – 2 Does TXA reduce the risk of
intracranial bleeding in patients with TBI? BMJ
2011
• 250 of the 20,000 patients eligible.
• Brain haemorrhage growth 5mm vs. 8mm (TXA vs. placebo)
• Not SS
• No mention of extent of extracranial injuries in either group
making mortality comparisons difficult
• Not well matched as there were more pts with SAH (61% vs
43%)
• No increase is focal cerebral ischaemia
• Conclusion “it is probable that benefits of tranexamic acid
outweigh risks’

Trauma Haemorrhage
1. Coagulation monitoring and measures to support
coagulation should be implemented early
2. Damage control surgery
3. Physiological targets, suggested use & dosing of
fluids, blood products and TXA
4. Patients on antiplatelet agents and/or oral
anticoagulants require special attention
5. Mutlidisciplinary approach & evidence based
protocols adapted to local circumstances need to be
developed and implemented

Fluids
• Don’t give too much
• Don’t give too little
• Make sure you give the right
amount
• Starches bad…very bad
Association of HES administration with mortality and AKI
in critically ill patients requiring volume resuscitation.
Meta-analysis. JAMA 2013 vol 309 (7)
• Albumin back in?
SAFE subgroup analysis 1200 pts with severe sepsis - 28/7
mortality lower in albumin group (30% vs. 35% OR 0.87)
Finfer S et al 2011 Intensive Care Med 37:86–96
Delayney metaanalysis. Role of albumin as a
resuscitation fluid for patients with sepsis. 17 studies,
1977 patients. Crit Care Med 2011
Albios Study – Gattinoni (video ion ESICM website)
“lets talk about fluid
responsiveness”
NO!

ESICM statement on colloids
1. Recommend not to use HES with mw ≥ 200kDa in
patients with severe sepsis or risk of AKI
2. Suggest avoid 6% HES or gelatin in these groups
3. Recommend not to use colloids in patients with head
injury and not to administer gelatins and HES in orhan
donors
4. Suggest avoid hyperoncotic solutions for fluid
resuscitation

ALBIOS
• RCT, 100 ICUs in Italy
• Aug 2008 – Feb 2012
• 1818 patients with severe sepsis
• 300mls 20% HAS daily to maintain serum albumin at 30g/dl + CSL vs.
CSL
• Primary outcome: mortality at 28d
– HAS + CSL: 31.8%
– CSL: 32%
• Secondary outcomes: 90 d mortality
– No difference

6S 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%
-

CHEST 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
-

CRISTAL Study
• 2857 sequential ICU patients 2003-2012 57
ICU’s
• Colloids vs CSL for all fluid interventions
other than maintenance
• Colloids
– Reduced mortality at 28d & 90d
(25% vs 27% & 30% vs 34%)
– More days alive without MV
– More days alive without vasopressors
– Less RRT
-

Need a nice summary?
Open Access!
#FOAMcc

CALORIES
• Open, multicentre, RCT
• 2400 patients in 33 ICUs in UK
• PN vs. EN within 36 hours for 5/7
– All cause mortality 33.1% (PN) vs. 34% (EN)
• Secondary outcome:
– Vomiting more in EN
– No difference on other 16 outcomes including
‘serious’ hypoglycaemia
– NB daily calorific targets achieved in <40% in
both groups

The SuDDICU study
SDD
12 meta-analyses of 28 RCT’s.
10 show reduced pneumonia
rate; 6 show morality benefit
• Why have clinicians avoided
implementing it in UK?
• What are the barriers?
• What further evidence is
required before full scale
clinical implementation

VITdAL-ICU
• RCT, Single Centre with 5 ICUs in
Austria, 475 patients
• Vit D or placebo
– Hospital LOS no different
• Secondary outcome. No difference:
– ICU LOS
– ICU-, 28d- , hospital- & 6 month- mortality
• Subgroup analysis
– If severe vit D def and given Vit D3 -> improvement
in 28d- hospital- and 6 month- mortality

Systematic review: CCM 2010
In those patients
receiving enteral
nutrition, stress ulcer
prophylaxis may not be
required and may
actually increase VAP

H2R antagonists vs PPI
• Cohort Study of 35,000
pts
• MV > 24 hours and either
H2R antagonist or PPI
• H2R antagonist group
had
– Less GI haemorrhage 2.1
vs 5.9%
– Pneumonia 27% vs 39%
– C.Diff 2.2% vs 3.8%

Hepatology
• ALD
Alcohol related illness costs NHS £1.7
billion/year
Systematic review of 21 articles
Overall ICU mortality 40-50%
Mackle study only one to provide data
on GI haemorrhage - mortality 48%,
62%, 67%,68% for unit, hospital, 6/12
and one yr - if get out of hospital most
will survive
Organ support - 3 papers (ventilation,
vasoactive drugs, RRT)
Mackle -
- if MV and vasoactive drugs hospital mortality 86%
- If MV, vasoactive drugs and RRT > 90%
- If just MV 31%
Saliba RRT 90%
Rye 100% mortality if require RRT

STOPAH
• RCT, 65 UK Hospitals
• 1103 patients with alcoholic hepatitis
• Primary outcome: mortality at 28 days was not
statistically different between any individual
group – p-value for drug interaction was 0.41
• Prednisolone + placebo: 14.3%
• Pentoxifylline + placebo: 19.4%
• Prednisolone + pentoxifylline: 13.5%
• Placebo: 16.7%
• Secondary outcome. No difference:
– ICU LOS
– ICU-, 28d- , hospital- & 6 month- mortality
• Subgroup analysis
– If severe vit D def and given Vit D3 -> improvement in 28d- hospital-
and 6 month- mortality

Intraabdominal pressures
http://www.wsacs.org/

DESTINY II
• RCT 13 hospitals in Germany
• MCA infarct with NIHHS > 14
• Decompressive craniotomy vs standard ICU treatment
• Primary outcome: score of 0-4 on Modified Rankin Scale
at 6 months
• 20/49 in hemicraniectomy group vs. 10/63 in control
group
• Bias-corrected, adjusted for the sequential nature of the
trial
• 38% vs. 18%, OR 2.91 (95% C.I. 1.06-7.49, P=0.04)
• Early hemicraniectomy significantly increased probability
of survival in patients >60 years of age with malignant
MCA infarction, but most survivors had substantial
disability

Neuro-ICU
ICP Monitoring
• Multicentre RCT of 324
patients Bolivia and
Ecuador
• Intraparenchymal ICP
monitoring vs. clinical &
imaging
• No difference in mortality
or neuropsycholoigcal
status at 6/12
A Trial of Intracranial-Pressure
Monitoring in Traumatic Brain Injury
Randall M. Chesnut et al
N Engl J Med 2012; 367:2471-2481

CATIS
• 4,071 patients
• Within 48 hrs ischaemic stroke
• nonthrombolysed and ↑BP
• Hypertension therapy vs no BP Rx
• BP control effective
• No difference
– death and major disability
• 14 days / hospital discharge
• 3 months

INTERACT 2
• 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

Magnesium for aneurysmal SAH (MASH-2): a randomised
placebo-controlled trial 
Mees S et al. 2012 The Lancet. Vol 380 9834:44-49
• 8 ICU’s in Europe and S America
• 1204 patients
• The question: does Mg reduce poor
outcome by reducing vasospasm
and delayed cerebral ischaemia
(DCI)
• Magnesium 64mmol/day for 20/7
or placebo
• Primary outcome of poor outcomes
as defined by score 4-5 on
modified Rankin Scale at 3/12, or
death
• NO DIFFERENCE

Delirium
HOPE ICU
• 142 patients with delirium
• CAM-ICU assessment
• Double blinded
• Haloperidol vs. placebo
• No change in duration of
delirium in critically ill patients
• Haloperidol should be reserved
for short term management on
acute agitation
Effect of intravenous
haloperidol on the duration
of delirium and coma in
critically ill patients (Hope-
ICU): a randomised,
double-blind, placebo-
controlled trial
Valeirie Page. The Lancet Respiratory Medicine, Volume
1, Issue 7, Pages 515 - 523, September 2013

Treating Delirium
101 MV patients RCT
haloperidol vs. ziprasidone vs placebo
21/7 study period
No difference in any of the groups!

The beginning; Kress NEJM 2000 Reduction
in LOS
Girard Lancet 2008
Decreased ICU stay, time on ventilator and
mortality
Strom Lancet 2010
Reduction in LOS and ventilator days
No sedation group - boluses of morphine, well established in
institution, more agitated delerium in no sedation group
Jacob JAMA 2012 PRODEX/MIDEX
No better than midaz or propofol at
maintaining light to mod sedation and more
adverse effects. Increased patient
interactions. Less vent days than midazolam
Ryker JAMA 2009
Reduction in ventilator days and delirium
Mehta 2013
For MV patients managed with protocolised
sedation, the additon of daily sedation
interruption did not reduce duration MV or ICU

Don’t forget the simple things….
• Small RCT 136 patients
• Used NEECHAM score
• Delirium (20%) similar
but less mild confusion
with ear plugs and good
night sleep <50% vs. 25%

Guidelines for managing delirium

Functional disability 5 years after ARDS
109 survivors from ’98 - ’01
Interview, PFT’s, 6 min walk
test, resting & exercise
oximetry, chest imaging, QOL
survey
PFT’s normalish
BUT 6 min walk test 76%
predicted, physical/
psychological problems

Microbiology
• 96 ICU’s
• Data from 60,000 admissions ’09-’11
• Invasive fungal disease defined as BC
or sample from normally sterile site
showing yeast/mould cells in a
microbiological or histopathological
report
• 383 (0.6%) were admitted with or
developed IFD
• Conclusion:
Incidence of IFD in non-neutropenic,
critically ill patients is low

4 steps to keep up with the literature after the
exam
Sign up to criticalcarereviews.com
Check out emlitofnote.com, The Bottom Line & LITFL, ScanCrit
& icmcasesummaries
Get a twitter account and follow #FOAMcc & #FOAMed http://
www.wessexics.com/Wessex_ICM_Blog/files/5af570b612a8f22d6841f96179a2fc92-16.html
Podcasts – emcrit, RAGE, St.Emlyns, CRIT-IQ, PHARM, JICScast,
FOAMcast, Critical Care Practitioner

Best of Luck!
@stevemathieu75
wessexics.com portsmouthicu.com

Hot Topics in ICM - PINCER Course 25th sept 2015

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Hot Topics in ICM - PINCER Course 25th sept 2015

Similar to Hot Topics in ICM - PINCER Course 25th sept 2015 (20)

More from Steve Mathieu

More from Steve Mathieu (16)

Recently uploaded

Recently uploaded (20)

Hot Topics in ICM - PINCER Course 25th sept 2015