hot topics in critical care

Academic Department of Critical Care Queen Alexandra Hospital Portsmouth

Hot Topics in ICM@stevemathieu75 Consultant in Intensive Care Medicine

Queen Alexandra Hospital, Portsmouth

23rd September 2016

• International, multicenter RCT• 52 centres (mostly UK)• 408 patients randomised• Decompressive craniectomy vs. Medical

management (barbiturates) if ICP > 25mmHg

• Outcomes: death and GOS-E at 6 & 12 m• Fewer deaths in surgical group 30% v 52%

(at 12m)• Estimated that for every 100 patients

treated with surgery: 22 more survivors. Of these 22

– 27% VS; 36% LSD; 36% USD or better

In patients with a traumatic brain injury (TBI) and refractory intracranial hypertension, does decompressive craniectomy, result in more favourable mortality and neurological outcomes at 6 months, compared with barbiturate coma and continued medical management?

Trial of Trial of Decompressive Craniectomy for Traumatic Intracranial HypertensionHutchinson. NEJM 2016

• RCT 47 centres, 18 countries• 387 patients• Therapeutic hypothermia (32-35C) for at least 48 hours and

continued until ICP controlled + standard care vs. standard care if ICP > 20mmHg > 5mins after stage 1 treatment

• Good outcome (GOS-E)– 25.7% in hypothermia group vs standard care group 36.5%

In patients with TBI, does hypothermia (32-35C) and standard care compared to standard care alone reduce death and major disability at 6 months after injury?

Trial of Trial of Decompressive Craniectomy for Traumatic Intracranial HypertensionHutchinson. NEJM 2016

• In moderate or severe TBI does EPO improve neurological outcome?• Neuroprotective effects ? Reduce apoptosis• RCT, 29 countries; 606 patients• 40000 IU of EPO x 3 vs. placebo• Neurological disability at 6/12 or mortality

– GOS-E 1-4: 44% vs 45%– 6/12 mortality 11% vs 16%– DVT 16% vs 18%

In patients with moderate or severe traumatic brain injury does the administration of erythropoietin compared with placebo improve neurological outcome at 6 months after injury?

Erythropoietin in traumatic brain injury: a double-blind randomised controlled trial

• International RCT• 1000 patients randomised if SBP > 180mmHg • Intervention:

– Target systolic BP 110 to 139 mmHg throughout the 24 hours after randomisation vs.– Target systolic BP 140 to 179 mmHg throughout the 24 hours after randomisation– Nicardipine and labetalol in both groups

• Primary outcome: Proportion of patients who had modified Rankin scores 4 to 6 at 3 months (significant disability or death)

– No difference between groups (38.7% in intervention, 37.7% in control)

• Secondary outcome: – No difference in death, haematoma volume at one week – Intensive group 5% more likely to develop AKI

• NB trial halted at 1000 patients because of futility

http://pulmccm.org/main/2016/n-engl-j-med-review/blood-pressure-goals-intracerebral-hemorrhage-atach-ii/

In patients with acute intracerebral haemorrhage and who are hypertensive, does rapid lowering of systolic blood pressure compared to standard therapy improve patient outcomes ?

Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

• 18 UK ICUs’ • 2 x 2 factorial design• 421 patients randomised• Intervention:

– Study Drug 1: Vasopressin (titrated up to 0.06 U/min) or Norepinephrine (titrated up to 12 μg/min)– Study Drug 2: Hydrocortisone (50mg 6 hourly and then weaned) or Placebo– If the patient was still hypotensive after the first dose of study drug 2 then additional open-label

catecholamine vasopressors could be administered

• Open labelled vasopressor was permitted for up to 6 hours before enrolment to this study. Once study drug one was commenced, the open labelled vasopressor was weaned off as quickly as possible

• Primary outcome: the number of days alive and free of kidney failure at 28/7– Around 55-60% for all groups

• Fewer patients required RRT in the VA group compared with the NADR group. These patients were mostly the non-survivors

Does early vasopressin use reduce the risk of kidney failure in patients with septic shock compared with norepinephrine?

Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock

• RCT 15 ICUs Australia• Is Dexmedetomidine effective in reducing the incidence of agitated delirium and

days on a ventilator?• Adult ICU patients who needed to remain mechanically ventilated because their

degree of agitation was considered so severe as to make lessening their sedation and extubation unsafe

• Primary outcome: Statistically significant increase in median ventilator free hours at 7 days in the dexmedetomidine group 144.8 vs. 127.5 hours, P=0.01

• Patients in the placebo group received significantly more antipsychotics meds (65.6% vs 36.8%, 95% CI -51.3,-6.3%, p=0.02), more opioid, and a significantly higher dose of propofol for the 7-days after randomisation.

Is Dexmedetomidine effective in reducing the incidence of agitated delirium and days on a ventilator?

Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients with Agitated Delirium

• RCT. 31 ICUs in France• 620 patients• Initiation of RRT within 6 hours vs

later following confirmation of KDIGO stage 3

• Primary outcome: mortality at 60 days – no significant difference

– 48.5% in early vs. 49.7% in delayed, P=0.79

In critically ill patients with acute kidney injury does delayed compared with early initiation of renal replacement therapy (RRT) reduce mortality at 60 days?

Initiation Strategies for RRT in the Intensive Care Unit

• RCT. Single centred• 230 patients• 5 inclusion criteria including KDIGO

stage 2• Initiation of RRT within 8 hours vs 24

hours of confirmation of KDIGO stage 2

In critically unwell patients with acute kidney injury, does early initiation of renal replacement therapy (RRT) compared to delayed initiation reduce all cause mortality at 90 days?

Effect of Early vs Delayed Initiation of RRT on Mortality in Critically Ill Patients With Acute Kidney Injury

• French multicentre RCT• 380 patients• Acetazolamide vs placebo for up to 28d to patients with COPD and a metabolic

alkalosis (primary or mixed), receiving invasive mechanical ventilation• Primary outcome: No statistical difference in the median duration of invasive

ventilation between groups– 136.5 hours (IQR 68.7 – 234.7 hours) in the acetazolamide group vs. 163.0 hours (IQR 86.2 – 242.9

hours) in the placebo group; P=0.17

• Daily median serum bicarbonate change (mEq/L)– Reduction in bicarbonate in acetazolamide group: -0.3 vs. 0.3; P=<0.001

• Median number of days with a metabolic alkalosis was fewer in acetazolamide group– 2 vs 4 days; P=<0.001

Does acetazolamide reduce the duration of mechanical ventilation in critically ill patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis?

Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients with Chronic Obstructive Pulmonary Disease

• RCT 23 ICU’s in Oz/Nz. 700 patients• 1g paracetamol 6 hourly vs placebo up to 28 days • ?immunomodulatory• Median ICU-free days to day 28: no significant difference

– 23 (IQR 13-25) in the paracetamol group vs 22 in the placebo group (IQR 12-25) CI 0-1; P=0.07

• all cause mortality at 28 days– no significant difference13.9% vs 13.7%

• all cause mortality at 90 days– no significant difference15.9% vs 16.9%

• Liver dysfunction necessitating stopping study drug– lower in paracetamol group8.1% vs 9.9%

Does the regular administration of paracetamol to critically ill patients with fever and known or suspected infection, affect the number of ICU-free days?

Acetaminophen for Fever in Critically Ill Patients with Suspected Infection

In critically ill patients, does the use of a balanced crystalloid solution compared to normal saline effect the incidence of acute kidney injury?

Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomised clinical trial

• RCT 4 ICU’s in Oz/Nz. 2278 patients• 0.9% NaCL vs Plasmalyte (median 2000mls each) • Primary outcome: proportion of patients with AKI based

on RIFLE criteria (‘injury’ or greater and based solely on creatinine component) within 90 days of enrolment: no statistical difference

- 9.6% in intervention group vs 9.2% in control group; P=0.77

• Secondary outcome: Plasma-Lyte 148 vs. 0.9% sodium chloride – no statistical difference in any of the following:- RRT requirement; mechanical ventilation; LOS; all cause mortality

NEW DEFINITION SEPSIS life-threatening organ dysfunction caused by a dysregulated host response to infection

Septic Shock: Sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65mmHg and having a serum lactate level >2mmol/L (18mg/dL) despite adequate volume resuscitation.

Sepsis 3

Organ dysfunction = acute change in total SOFA score ≥2 points due to the infection (The baseline SOFA score can be assumed to be zero in patients not known to have preexisting organ dysfunction)

A SOFA score ≥2 = mortality risk of approximately 10%; Septic shock = mortality > 40%

Screening Patients ? Sepsis: Patients with suspected infection that are likely to have a prolonged ICU stay or to die in the hospital can be promptly identified at bedside with qSOFA. Less robust but no lab tests

Thanks to REBEL EM for images http://rebelem.com/sepsis-3-0/

The Sepsis Studies

Does cognitive function in TTM cardiac arrest survivors differ between the 33 and 36 degree groups and also compared with a cohort of patients who sustained STEMI but no cardiac arrest

•652 cardiac arrest survivors from TTM•Survival until 6/12 52%

- invited to follow up- about half had psychometric testing- compared with a control group (STEMI & PCI but no cardiac arrest)

•About 50% had cognitive impairment•33 vs. 36 vs. control group

- cognitive outcome no different between temperature groups- attention & mental speed more affected in cardiac arrest patients-- memory & executive functioning similar in all groups

Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After TTM at 33ºC Versus 36ºC

In organ donors, following diagnosis of BSD, does TH decrease delayed graft function in kidney recipients?

•2 organ procurement centres in US•RCT 394 donors•Mild hypothermia (Target 34 – 35C) vs Normothermia (Target 36.5 – 37.5C)•Delayed graft function

- the recipient’s requirement for dialysis during the 1st week post-transplantation- 28.2% vs 39.2%, P=0.008

Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After TTM at 33ºC Versus 36ºC

In paediatric patients with septic shock, does adrenaline compared with dopamine reduce 28 day mortality?

•RCT; single centre Brazil•120 patients•Adrenaline vs dopamine after 20mls/kg bolus •Once 60mls/kg fluid given, if still shocked, clinician choice of vasoactive drug •28 day mortality

- Adrenaline group vs Dopamine group 0.7% vs 20.6%

Double-Blind Prospective Randomized Controlled Trial of Dopamine vs Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock

CALORIES• Open, multicentre, RCT• 2400 patients in 33 ICUs in UK• PN vs. EN within 36 hours for 5/7• Primary outcome:

– 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


In adult patients with alcoholic hepatitis, does prednisolone and / or pentoxifylline compared to placebo reduce mortality?

•RCT 65 UK hospitals•Pentoxyfylline + placebo vs. Prednisilone + placebo vs. both vs placebo x 2•ICUs in Canada and France; 2510 patients•28d mortality no statistical difference

STOPAH: Prednisolone or Pentoxifylline for Alcoholic Hepatitis

• In ICU patients who require a CVC, does the choice of insertion site affect the complication rates?

• 10 ICUs in France (4 university hospitals and 5 general hospitals)• SC, IJ or femoral (>1000 lines in each group)• Composite measure of CRBSI and DVT• SC = lower infection; higher PTX


PERMIT

• Is “fresh” blood (stored for 8 days or less) better than old (stored 2-42 days)?• RCT 64 ICUs in Canada and France; 2430 patients• RBCS: 6 days vs 22 days• 90 day mortality (37% vs. 35%) • Transfusion triggers and processes for safe administration of blood are probably

more important


PERMIT

TRISS• RCT 32 general ICUs in Scandinavia• 998 patients with septic shock & Hb <9• Transfusion threshold <7 vs. <9• Excluded patients with ACS• Mortality at 90 days (43% vs 45%)• Secondary outcomes

• Vasoactive drugs• Ventilation• RRT• % of days alive & out of hospital• Ischaemic events


TITRe2• In adults undergoing cardiac surgery, does a

restrictive transfusion strategy vs liberal one lead to fewer infections and ischaemic events within 3 months?

• RCT 17 cardiac ICUs in UK• Trigger Hb 75 vs 90g/dl• Composite outcome of serious infections or

ischaemic events within 3/12 – 35% vs 33%

TRICC, TRISS, Villanueva


PROPPR• RCT in 12 N. American Level 1 trauma centres• 680 patients• 1:1:1 vs. 1:1:2 FFP / plt / PRBCs• 24 hour and 30d mortality no different • 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



Guidelines

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

SMRScoring Systems

•Definitions: CPIS, CDC, HELICS•Pathogens:

- Early: strep pneumonia; H.influenzae; MSSA; Klebsiella, E.Coli- Late: MRSA, acinetobacter, pseudomona

•Elevation of head of bed (30-45 degrees)•Daily sedation interruption and assessment of readiness to extubate•Use of subglottic secretion drainage•Avoidance of scheduled ventilator circuit changes•? Stress ulcer prophylaxis•? Avoid oral chlorhexidine

• Reduces nosocomial pneumonia in cardiac surgery• Meta-analyses showing benefit heavily influenced by cardiac patients• No benefit for VAP in general ICU’s

•ICUs in Canada and France; 2510 patients•28d mortality no statistical differencehttps://ccforum.biomedcentral.com/articles/10 .1186/cc13775

ICS Recommended bundle of interventions for the preventionof ventilator associated pneumonia

NAP 4 - 2011• All NHS hospitals for 1 year ’08-’09• 184 reports

133 anaesthesia36 ICU15 ED

• Inclusion criteria death, brain damageemergency surgical airwayunanticipated ICU admissionProlongation 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 CapnographyAirway equipmentBack up planningStaffingPatient transfersEducation/trainingTracheostomy tube designTeam working


Tracheostomy standards• Indications for tracheostomy• Cautions and contraindications• Consent• Equipment• Ultrasound• Anaesthesia • Staffing• Types of tracheostomy tubes• Inner cannulae• Complication

– Early– Late– Airway emergencies

Antibiotic Stewardshiphttps://www.ficm.ac.uk/sites/default/files/FICM-Start_Smart_Then_Focus_FINAL.pdf

https://www.ficm.ac.uk/sites/default/files/FICM-Start_Smart_Then_Focus_FINAL.pdf

Community Acquired Pneumoniahttps://www.nice.org.uk/guidance/cg191/chapter/1-Recommendations#community-acquired-pneumonia-2

https://www.nice.org.uk/guidance/cg191/chapter/1-Recommendations#community-acquired-pneumonia-2

https://www.nice.org.uk/guidance/cg191/chapter/1-Recommendations#community-acquired-pneumonia-2

Brain Trauma Foundation Guidelines 22nd Sept 2016https://braintrauma.org/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed#/:guideline


http://www.britishinfection.org/files/5614/5674/2938/McGill_meningitis_guidelines_Final_published_proof.pdf

Guidelines for managing delirium


Designing a new Intensive Care Unit

Fire on the ICU

1. Protect patients and staff2. Manage fire hazard3. Identify cause and prevention

Management of Fire Hazard – RACER

RESCUE

ALERT

CONTAIN

EXTINGUISH

RELOCATE

Care of the dying patients (2015)https://www.nice.org.uk/guidance/ng31

Rehabilitation after Critical Illness (2015)https://www.nice.org.uk/guidance/cg83

AKI: Prevention, Detection and Management (2013)https://www.nice.org.uk/guidance/cg169

AF Management (2014)https://www.nice.org.uk/guidance/cg180

https://www.nice.org.uk/guidance/ng31

https://www.nice.org.uk/guidance/cg83




Useful resources

Neuro


http://www.neuroicu.org.uk/

The SAH section definitely worth a read for the exam

Critical Care Reviews


2014 & earlier

ALBIOS

• RCT, 100 ICUs in Italy• 1795 patients with severe sepsis• 300mls 20% HAS daily + CSL vs. CSL• Target serum albumin 30g/dl • 287 mortality: no different

– HAS + CSL: 31.8%– CSL: 32%

• Secondary outcomes: 90 d mortality– No difference


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


CALORIES• Open, multicentre, RCT• 2400 patients in 33 ICUs in UK• PN vs. EN within 36 hours for 5/7• Primary outcome:

– 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


PEITHO• RCT; 13 countries; 1006 patients• Tenecteplase vs placebo• Death or haemodynamic decompensation

within 7 days – Significantly lower in thrombolysis group– 2.6% vs. 5.6% in placebo group (NNT 34)

• Mortality at 7 days and 30 days– 7 days: 1.2% vs. 1.8%; 30 days: 2.4% vs. 3.2%

• Major extracranial bleeding - higher in thrombolysis group – 6.3% vs. 1.2% (NNH 19)

• Haemorrhagic stroke – higher in thrombolysis group – 2% vs 0.2% (NNH 55)


HARP 2

• 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


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


CRISTAL Study• Stratified open label RCT • Recruitment over 9 years• Any colloid vs any CSL• 2857 patients with hypovolaemic shock • 28 day mortality• Colloids favoured:

– 90 day mortality (30% vs 34%)– More days alive without MV– More days alive without vasopressors– Less RRT

-



http://www.britishinfection.org/files/5614/5674/2938/McGill_meningitis_guidelines_Final_published_proof.pdf


Themes

NAP 4 - 2011• All NHS hospitals for 1 year ’08-’09• 184 reports

133 anaesthesia36 ICU15 ED

• Inclusion criteria death, brain damageemergency surgical airwayunanticipated ICU admissionProlongation 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 CapnographyAirway equipmentBack up planningStaffingPatient transfersEducation/trainingTracheostomy tube designTeam 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%


ARDS - lots of trials

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


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 • No difference in

– 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. Dose2. Initiation of treatment3. Course length 4. Not all studies report adverse events


Functional disability 5 years after ARDS

109 survivors from ’98 - ’01Interview, PFT’s, 6 min walk test, resting & exercise oximetry, chest imaging, QOL surveyPFT’s normalishBUT 6 min walk test 76% predicted, physical/psychological problems


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 childrenAfshari Cochrane review 2007 - adultsBarrington Cochrane review 2010 – childrenAfshari – 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 trialGoodacre et al Lancet 2013 Vol 1 (4) 293-300


• In ICU patients undergoing intubation does apnoeic oxygenation during laryngoscopy increase the lowest arterial oxygen saturation experienced by patients

• Single centre• HFNC + other NRBM/BiPAP/BVM/standard nasal vs. NRBM/BiPAP/standard

nasal cannulae• Median lowest SpO2


PERMIT

• 12 French ICU’s; 310 patients• ‘ALI’• NRB vs HFNC vs NIV• 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


PERMIT

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


Tracheostomy standards• Indications for tracheostomy• Cautions and contraindications• Consent• Equipment• Ultrasound• Anaesthesia • Staffing• Types of tracheostomy tubes• Inner cannulae• Complication

– Early– Late– Airway emergencies

MCA & DoLSDoLS• 3 cases in 2014


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 trialMees 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 trialValeirie Page. The Lancet Respiratory Medicine, Volume 1, Issue 7, Pages 515 - 523, September 2013


http://www.thelancet.com/journals/lanres/issue/vol1no7/PIIS2213-2600(13)X7010-9

Treating Delirium


101 MV patients RCThaloperidol vs. ziprasidone vs placebo21/7 study periodNo difference in any of the groups!

The beginning; Kress NEJM 2000 Reduction in LOS

Girard Lancet 2008Decreased ICU stay, time on ventilator and mortality

Strom Lancet 2010 Reduction in LOS and ventilator daysNo sedation group - boluses of morphine, well established in institution, more agitated delerium in no sedation group

Jacob JAMA 2012 PRODEX/MIDEXNo 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 2009Reduction 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 LOS

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


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 InjuryRandall M. Chesnut et alN Engl J Med 2012; 367:2471-2481

Neuro


http://www.wessexics.com/WICS_Guidelines/

The SAH section definitely worth a read for the exam

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

TTM• 950 unconscious adults; 36 ICU’s• 33°C (n=473) with 36°C (n=466)• No difference in

– All cause mortality33°C (50%) with 36°C (48%)– poor neurological function at

180 days33°C (54%) with 36°C (52%)


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%


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


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


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

ECMOStudy 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


Passive Leg Raise


• 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

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• No difference in

– 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• No difference in

– 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


ADRENAL


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 infectionsSprung 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

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

ABLE Multicentre UK RBC transfusion (7d vs. 15-25d)Transfusion triggers – TRICC, TRISS & Villaneuva, TITRe2PROPPR: Plasma, Platelets & PRBC’s 1:1:1 vs. 1:1:2Guidelines on the management of anemia and RBC transfusion in adult critically ill patients (BCSH Guidelines 2012)Serious Hazards of Transfusion (SHOT) – JICS July 2013

TRISS• RCT 32 general ICUs in Scandinavia• 998 patients with septic shock & Hb <9• Transfusion threshold <7 vs. <9• Excluded patients with ACS• Mortality at 90 days (43% vs 45%)• Secondary outcomes

• 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%)


TXACRASH - 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


TXACRASH – 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 early2. Damage control surgery 3. Physiological targets, suggested use & dosing of fluids, blood products and TXA4. Patients on antiplatelet agents and/or oral anticoagulants require special attention5. 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 2011Albios 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 AKI2. Suggest avoid 6% HES or gelatin in these groups3. Recommend not to use colloids in patients with head injury and not to administer gelatins and HES in orhan donors4. Suggest avoid hyperoncotic solutions for fluid resuscitation


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

-


Gastrointenstinal

• In patients with severe pancreatitis, does early enteral feeding compared with on-demand feeding reduce death or major infection?

• RCT; Netherlands; 208 patients• Early NJ within 24 hours vs IV fluids + ‘on demand’ • Composite outcome of death or major infection within 6 months


• In critically ill adults, does restriction of non-protein calories (permissive underfeeding) compared to standard feeding reduce mortality at 90 days?

• RCT; Saudi Arabia and Canada; 894 patients• Permissive enteral underfeeding (40-60%) vs standard (70-100%) for up to 14

days• ? Moderate survival benefit from permissive underfeeding with moderate

caloric intake (around 50% of target calories) and maintenance of full protein requirement (1.2-1.5g per kg per day)


PERMIT

Need a nice summary?


The SuDDICU studySDD

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 • Primary outcome:

– 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

• ALDAlcohol 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


Intraabdominal pressures

http://www.wsacs.org//

http://www.xigris.com/

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


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