Trials

Question 1

ALBIOS

Answer 1

2014 n= 1800 Italian

Severe sepsis or septic shock
Does keeping albumin >30g/L improve mortality

No difference in 28 or 90 day mortality

Albumin group less time on vasoactive drugs and improved CVS parameters earlier in admission

No difference in SOFA score

Higher incidence on coag and liver dysfunction in albumin group

Question 2

TRICS III

Answer 2

cardiac surgery patients
restrictive vs liberal transfusion practices

Restrictive was non inferior
- patients ok with Hb down to 75

Question 3

LeoPARDS

Answer 3

2017
n = 500, multicentre

use of levo in sepsis
No improvement in mortality or SOFA scores

increased risk of arrythmias and longer MV

Question 4

EAT ICU

Answer 4

2017
does early goal-directed nutrition (EGDN) during ICU stay compared to standard care nutrition delivery result in improved physical quality of life at 6 months

n = 200, single centre

used indirect calorimetry and urinary urea excretion to calculate needs, and 100% provided (with EN +PN as needed)

No difference in outcomes at 6/12

Question 5

RECONNECT

Answer 5

OUtcome - In critically ill patients who pass a spontaneous breathing trial, reconnection to a ventilator for 1-hour compared with immediate extubation, significantly reduced the rate of re-intubation within 48 hours.

However - very underpowered

Question 6

DETO2X - AMI - use of oxygen in suspected MI patients

Answer 6

n =>6000

Question - In patients with suspected myocardial infarction with no baseline hypoxia (sats >90%), does oxygen therapy or room air improve all-cause mortality at 1 year?

patients given 6l/min for 6-12hrs vs air

• supplemental oxygen made no difference to outcomes in normoxic patients with suspected AMI
• This result combined with other recent studies that have suggested potential harm from oxygen, plus the fact oxygen is not free, suggests that oxygen therapy in this population is no warranted

Question 7

IVC collapsability in spont breathing critically ill and fluid responsiveness

Answer 7

Background - Assessing the collapsibility (or distensibility if the patient is mechanically ventilated) of the IVC during respiration using point of care ultrasound (POCUS) has been recommended by some clinicians as a means to assess fluid responsiveness, however this is controversial

Did find it identified patients who resonsded, BUT was a poorly deigned study with bad methodology

Question 8

Use of HFNP in high risk patients following extubation

Answer 8

Background -
Hernandez has previously demonstrated that in low risk patients the risk of re-intubation can be decreased with the use of high-flow nasal oxygen post-exubation

Nava and Ferrer reported that in high risk patients, the use of post extubation non-invasive ventilation can reduce re-intubation rates and respiratory failure

Bottom line -
- This randomised controlled trial demonstrated that in patients that are high risk for re-intubation the use of high flow nasal oxygen was non-inferior to non-invasive ventilation

My practice -
In patients that are high risk for re-intubation I will use non-invasive ventilation, and if this not tolerated then change to high flow nasal oxygen

Question 9

TRICOP

Answer 9

Restrictive vs liberal transfusion in cancer patients

No difference in 28 or 60 day mortality, but a difference in 90 days (BUT fragility index of 0)

Question 10

ATHOS III

Answer 10

NEJM 2017

In patients with refractory vasodilatory shock does the addition of angiotensin II improve blood pressure compared with standard vasopressor therapy?

Bottom line -
Angiotensin II increases blood pressure in patients with vasodilatory shock
Numerically patients were less likely to have adverse events and die compared with the control group
This trial is likely to make angiotensin II available (the trial was conducted in consultation with the FDA)

Question 11

DESIRE

Answer 11

Question - In ventilated patients with sepsis, does a sedation strategy with dexmedetomidine compared with no dexmedetomidine improve mortality and number of ventilator-free days?

The Bottom Line
In ventilated patients with sepsis or pancreatitis, this study fails to demonstrate a significant impact of dexmedetomidine on 28-day survival or ventilator-free days but was likely underpowered for mortality.

Question 12

Levosimendan for Hemodynamic Support after Cardiac Surgery

Landoni. NEJM 2017

Answer 12

In patients undergoing cardiac surgery with peri-operative left ventricular dysfunction, it appears that a low-dose infusion of levosimendan is not beneficial

NB - didn’t use bolus, used much smaller doses for infusion

Question 13

Levo CTS

Answer 13

Used prophylactically in CTS patients with LVEF <35%

Levosimendan does not have any clinical outcome benefit, when used as a prophylactic agent, in patients with poor left ventricular ejection fraction undergoing cardiac surgery on bypass
- used a low dose infusion and small bolus

Question 14

Use of NIV upto 7 days after abdominal surgery in those who develop respiratory failure

Answer 14

Patient with hypoxia and acute resp distress up to 7 days after surgery

In this trial, 6 hours of low-level non-invasive ventilation in patients with acute hypoxic respiratory failure after major abdominal surgery reduced the need for re-intubation compared to standard oxygen therapy

no clinically relevant harm or intolerance was identified and therefore this paper will change my practice

Further studies comparing this strategy to high-flow nasal oxygen therapy are urgently needed

Question 15

PRESERVE

Answer 15

NEJM 2017
high risk patients having interventional radiology
Does NAC or bicarb improve outcome

NO

Question 16

terlipressin in cirrhosis and septic shock

Answer 16

In patients with cirrhosis and septic shock, this single centre non-blinded RCT demonstrated that terlipressin in comparison with noradrenaline improved haemodynamics and had a mortality benefit. Due to a number of methodological flaws and baseline differences I would want further evidence before this becomes standard practice.

Question 17

Hybernatus

Answer 17

Hypothermia for Neuroprotection in Convulsive Status Epilepticus NEJM 2016

Intervention
Target core temperature of 32 to 34°C as rapidly as possible post randomisation
Target temperature maintained for 24 hours

Conclusions
In critically ill patients with convulsive status epilepticus receiving mechanical ventilation, the addition of therapeutic hypothermia to standard antiepileptic therapy showed no significant benefit with respect to good functional outcome

Question 18

Dexmedetomidine for prevention of delirium in elderly (>65 yrs) patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial

Answer 18

Study drug started - low dose Dexmedetomidine
0.1mcg/kg/hr
If extubated: usually within 1 hour of admission to ITU post-operatively
If intubated: once sedation titrated to Richard-Agitation Sedation Score (RASS) -2 or higher

This study demonstrates an impressive reduction in post op delirium with low dose Dexmedetomidine infusion. Further studies needed to clarify if these results can be applied to a wider range of patients, and also to rule out possible safety concerns.

Question 19

Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients – RENAL trial NEJm 2009

Answer 19

Delivering higher intensity dialysis dosing is not without risk. Some of the potential disadvantages are; disturbance in electrolyte concentrations, increased costs and nursing workload, micronutrient depletion and subtherapeutic levels of antibiotics.

This is the best trial examining ‘dose’ of dialysis in critically ill patients and stands the test of time, even 8 years after publishing. I will continue my practice of dialysing critically ill patients with AKI at 25ml/kg/hr.

Question 20

Normal Oxygenation Versus Hyperoxia in the Intensive Care Unit (ICU) (OXYGEN-ICU)
Giradis. JAMA 2016

Answer 20

Question - In critically ill adults, does conservative oxygen therapy compared to liberal oxygen therapy reduce mortality?

94-98% vs >97%

Significantly lower mortality in conservative group
- need a larger RCT, avoid hyperoxia?

Question 21

PATCH lancet 2016

Answer 21

In patients with acute intracerebral haemorrhage, associated with antiplatelet therapy, does platelet transfusion compared with standard care reduce death or dependence?

No - worse outcomes (small trial, but still…)

Question 22

RESCUE ICP

Answer 22

Inclusion: patients with a TBI with an abnormal brain CT and raised intracranial pressure of >25mmHg for 1-12 hours, despite stage 1 and 2 measures; aged between 10 and 65 years

Intervention
Decompressive craniectomy
Continued stage 1 and 2 treatments plus decompressive craniectomy
Either large unilateral fronto-temporoparietal craniectomy (hemicraniectomy) for patients with unilateral hemispheric swelling or bifrontal craniectomy for patients with diffuse brain swelling

Improved mortality but worse functional outcome

Question 23

EUROtherm3235

NEJM 2015

Answer 23

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

In patients with ICP >20mmHg after TBI Cooling leads to worse mortality and functional outcome

Question 24

VANISH NEJM 2016

Answer 24

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

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

Bottom line -
- vasopressin does not reduce the number of renal replacement free days or mortality rate, and there was no clinical interaction with corticosteroids

Question 25

Procainamde vs amioderone in tretment of HD tolerated wide complext tachycardia

Answer 25

The results of this trial suggest an improved safety profile and efficacy of 10mg/kg intravenous procainamide over 20mins when compared with 5mg/kg intravenous amiodarone over 20mins in tolerated wide complex tachycardia.

Question 26

Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage
NEJM 2016

Answer 26

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

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

The Bottom Line
The results of this trial and that of the INTERACT2 trial do not support an early, intensive control of systolic blood pressure in patients with acute intracranial haemorrhage

Question 27

ELAIN-
Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury
JAMA 2016

Answer 27

Intervention
Initiation of RRT within 8 hours of confirmation of KDIGO stage 2

Control
- Inititation of RRT within 12 hours of either
KDIGO stage 3 criteria
Creatinine rise >3 fold increase from baseline, or oliguria <0.3ml/kg/hr for ≥24 hours or serum creatinine > 4mg/dl (353.6 μmol/l) with an acute increase of at least 0.5mg/dl (44.2μmol/l) within 24 hours
Absolute indication for RRT
Urea >100mg/dl
Potassium >6mmol/l and or ECG abnormalities
Magnesium >4mmol/l and/or anuria/absence of deep tendon reflexes
Blood pH <7.15
Urine production <200ml/12hr or anuria
Organ oedema in the presence of AKI resistant to diuretic treatment (defined as one trial of furosemide)

This single centre study demonstrates a significant reduction in 90 day mortality with early (stage 2 KDIGO) initiation of RRT, in a group of almost entirely surgical patients.

However, other evidence is conflicting

Question 28

AKIKI NEJM 2016
Initiation Strategies for Renal-Replacement
Therapy in the Intensive Care Unit

Answer 28

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

The Bottom Line
In critically ill patients with severe acute kidney injury, an early approach to RRT did not provide a mortality benefit compared to a delayed approach; when the RRT modality was predominately intermittent RRT.
~50% of the patients in the delayed group did not receive RRT
There was a significantly higher rate of catheter related nosocmial infections in the early group

Question 29

DahLIA

Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients with Agitated Delirium. A Randomized Clinical Trial
. JAMA 2016

Answer 29

Inclusion: 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

Bottom line -
This underpowered study showed potential benefits of using dexmedetomidine, in addition to standard care, for ventilated patients with agitated delirium, who are otherwise ready for extubation. In particular, there was a modest reduction in time for liberation from the ventilator, more rapid resolution of delirium and sedation and opioid sparing effects.

Question 30

ART

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA 2017

Answer 30

In patients with moderate-to-severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality
These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.

Done is south america
Use very high recruitment (upto 45cmH2O of PEEP)

Question 31

ATACAS TXA

Tranexamic Acid in patients Undergoing Coronary-Artery Surgery
N Engl J Med 2017

Answer 31

TXA 100mg/kg
Administered intravenously
30 minutes after induction
Dose reduced to 50mg/kg in January 2012 (1392 patients enrolled, 758 given TXA) as seizures reported and this was felt to be dose related

This trial provides valid reason to consider using TXA in elective patients undergoing elective coronary artery surgery to reduce the blood product requirements, however it may increase post-operative seizure incidence

Question 32

SHENFU critical care medicine 2017

Answer 32

This large multi-centre randomised controlled trial demonstrated a significant reduction in mortality with the use of Shenfu following in-hospital cardiac arrest, with a number needed to treat of 8
This compares to a NNT of 6 for the original HACA therapeutic hypothermia trial
The sceptic in me tells me that if something appears too good to be true then it probably is
My concerns regarding the lack of blinding, the differences in baseline characteristics, the variation in compliance with the post-resuscitation bundle and the fact that the study was performed in a single country means that I want to see more evidence before I start using Shenfu in my practice.

Question 33

TTM 48 JAMA 2017

Answer 33

In adults with out of hospital cardiac arrest (OOHCA) due to a presumed cardiac cause, who are post ‘return of spontaneous circulation’ (ROSC), does cooling to 33°C for 48 hours, compared with 24 hours, improve improved neurological outcomes at 6 months?

No improved outcome
High incidnce of hypotension and longer length of stay

I will continue to control temp for 24 hours following OOHCA

Question 34

INSTINCT intensive care medicine 2017

Answer 34

Clinical Question
In patients with necrotising soft tissue infection (NSTI), does the use of intravenous immunoglobulin (IVIG) compared to placebo improve patient reported physical outcomes?

Background
IVIG consists of pooled plasma from 2000-10000 donors with the IVIG fraction
IVIG has anti-infective and immunomodulatory properties. It inhibits the activity of streptococcal and staphylococcal virulence factors
NSTI’s are characterised clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality
Type 1: Polymicrobial: Anaerobic e.g. clostridium, non GAS, E Coli, klebsiella etc.
Type 2: Monomicrobial (GAS most common), staphylococcus, MRSA
Prior to INSTINCT, The effects of IVIG vs placebo have been assessed in only one small RCT. This was stopped early because of slow recruitment rate (21 patients). The evidence base for IVIG therefore comes mainly from retrospective studies

Negative study
This study does not demonstrate a statistically significant difference in patient centred outcomes when IVIG is used in combination with surgery, antimicrobials and hyperbaric oxygen

Question 35

Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure
Timsit J-F. JAMA 2016

Answer 35

Clinical Question
In critically ill patients with non-neutropenic sepsis, multiple Candida colonisation and multi organ failure, does empirical micafungin therapy increase invasive fungal infection-free survival at day 28 compared with placebo?

This study does not support empirical anti-fungal therapy with micafungin in a select group of intensive care patients at high risk of invasive candidiasis

Question 36

Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy
The Lancet 2017

Answer 36

Clinical Question
In high-risk patients receiving contrast medium, does prophylactic hydration with normal saline compared to no prophylaxis impact the rate of contrast-induced nephropathy?

Intervention - Hydration Group:
3–4 ml/kg/hr of normal saline for 4 hours before and after contrast OR 1 ml/kg/hr of normal saline for 12 hours before and after contrast

Control - No hydration

Authors’ Conclusions
No hydration was non-inferior to hydration in the prevention of contrast induced nephropathy. Hydration is more expensive and can cause problems in itself. HOWEVER - does not specify ICU patients; therefore, at this stage, intravenous hydration in this population should continue especially if the patient has haemodynamic instability, nephrotoxic drugs and high contrast doses. Patients with GFR < 30 should still receive peri-procedure hydration. With patients at risk of pulmonary oedema, hydration should be used judiciously.

Question 37

Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial
. Lancet Resp Med 2015

Answer 37

Intervention - Restricted caloric management group
20 kcal/h for at least 2 days and then a gradual return to normal intake protocol over the following 2-3 days

Restrictive caloric intake for refeeding syndrome did not statistically increase the number of days alive after ICU. However it did increase two clinically important components of this composite measure, survival time and 60-day mortality. In addition there were fewer respiratory infections. I will continue to use a restrictive caloric feeding regimen whilst treating refeeding syndrome

Question 38

Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock
Crit Care Med. 2015

Answer 38

The single centre randomised controlled trial in Brazil, demonstrated an increased mortality when dopamine, compared with adrenaline, was used to treat paediatric patients with septic shock. Patients treated with dopamine had a longer time until they were fully resuscitated, they had a greater need for renal replacement therapy, and greater number of hospital acquired infections. Further multi-centre trials are urgently needed to confirm these findings.

Question 39

Recovery after critical illness in patients aged 80 years or older
] Intensive Care Medicine 2015

Answer 39

Prospective cohort study in canada

The Bottom Line
Patients over 80 years old admitted to ICU for more than 24 hours have a poor recovery profile: 25% return to baseline after a year, 25% are alive but significantly worse than baseline and 50% are dead.
These data appear reliable and generalisable to most developed healthcare systems, and this might help guide communication and decision making with patients, families and referring clinicians.

Question 40

Air Versus Oxygen in ST-Segment Elevation Myocardial Infarction
AVOID. Circulation 2015

Answer 40

Clinical Question
In patients with ST-elevation-myocardial infarction (STEMI), without hypoxia, does receiving supplemental oxygen compared with no supplemental oxygen reduce early myocardial injury?

Intervention - Oxygen group; Patients received supplementary oxygen via face mask at 8L/min

Control group - no oxygen until sats <94%

The Bottom Line
This trial fails to show any benefit in giving oxygen to normoxic patients with STEMI undergoing PCI and may in fact cause harm

Question 41

PermiT: Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults
NEJM 2015

Answer 41

40–60% vs 70-100% of caloric requirement
- both had full protein diet

The bottom line -
Permissive underfeeding with full protein requirement appears safe in critically ill patients

Question 42

FLORALI: High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure
NEJM 2015

Answer 42

Clinical Question
In patients with acute hypoxaemic respiratory failure, does high-flow oxygen through nasal cannula, compared with standard oxygen delivered through a facemask or non-invasive positive-pressure ventilation, prevent intubation?

The Bottom Line
This study demonstrates that high-flow oxygen via nasal cannula is non-inferior to oxygen delivered by a non-rebreather facemask and BiPAP in reducing the subsequent need for intubation.
High flow oxygen reduces ICU and 90 day mortality compared with the other strategies. It also subjectively improves dyspnoea and respiratory discomfort at one hour compared with the other oxygen delivery devices.

Question 43

PROPPR: Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma. The PROPPR Randomized Clinical Trial
PROPPR Study Group*, JAMA. 2015

Answer 43

The Bottom Line
Among patients with severe trauma and major bleeding there was no significant difference in 24 hour or 30 day mortality in patients who received a blood product transfusion at a ratio of 1:1:1 compared to a ratio of 1:1:2. However the study was significantly underpowered for the observed difference in mortality found.
A ratio of 1:1:1 resulted in reduced mortality from exsanguination within the 1st 24 hours, with similar complication rates to a lower ratio protocol. Therefore, I will continue to aim for a 1:1:1 ratio in this population.

Question 44

Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial)
Resuscitation January 2015

Answer 44

Clinical Question
In patients who are in refractory cardiac arrest (>30mins, VF arrest if OOH, anything if in hospital), does protocolised management involving mechanical CPR, Hypothermia, ECMO and early reperfusion improve survival rate?

Single centre, australia

54% survival with good neurological outcome
The Bottom Line
The CHEER protocol has been shown to improve survival with favourable neurological outcome following cardiac arrest compared with historical data. It works and works very well in this experienced ECMO centre, with engagement of pre-hospital services and as part of a bundle. A multi-centre RCT is now required to determine if these impressive results can be replicated.

Question 45

PYTHON: Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis
N Engl J Med 2014

Answer 45

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

Intervention - “Early” group:
Nasojejunal tube placed within 24 hours of randomisation and feeding commenced
Tubes placed endoscopically or radiologically
Feeding was started at 20ml/hr for the first 24 hours, then 45ml/hr from 24-48 hours, then 65ml/hr from 48-72 hours, and full feeding based on actual body weight after this

Control - “On-demand” group:
Oral diet was provided at 72 hours
Supplementation by tube feeding after further 24 hours if unable to tolerate oral intake
Prior to this received only IV fluids unless they requested oral food

The Bottom Line
Allowing patients with severe pancreatitis three to four days to initiate oral intake appears to be safe and effective
This can reduce the discomfort, cost and complications associated with tube feeding in these patients
Although well-conducted this was a relatively small trial, and future data may change this picture

Question 46

DESTINY II: Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke
DESTINY II Investigators. NEJM 2014

Answer 46

Clinical Question
In older patients with malignant middle cerebral artery infarction does early hemicraniectomy, compared with standard care, improve survival without severe disability?

The Bottom Line
In older patients (>61) with malignant MCA infarction an early decompressive hemicraniectomy significantly improves mortality but leaves the vast majority of survivors with moderately severe or severe disability. This therefore leaves us with the difficult question of whether this treatment should be offered or performed.

Question 47

Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock
TRISS Trials Group. N Engl J Med 2014

Answer 47

The Bottom Line
In patients with septic shock and managed in an ICU setting, a transfusion threshold of 7g/dl compared with 9g/dl resulted in no difference in mortality or ischaemic events. This paper supports my current practice. Avoiding unnecessary blood transfusion removes the risk of infectious, immune and non-immune related complications as well as conserving this limited resource. However, in this study 10% of patients, in the low threshold group, received transfusions despite being above the treatment threshold, therefore there may be times when the threshold needs to be modified.
Patients with acute coronary syndromes were excluded from this trial.

Question 48

Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage – A Meta-analysis
2014 JAMA

Answer 48

The Bottom Line
Thrombolysis for PE is associated with a lower all cause mortality when compared to anticoagulation. This improvement is maintained in the subgroup of ‘intermediate risk’ PE with a NNT of 65. This is despite a significant increase in major bleeding in the thrombolysis group, with a NNH of 18. Of note, patients who were ≤65 years had no increase in major bleeding with thrombolysis.
With the MOPETT and TOPCOAT studies finding improved longterm outcomes with regards to pulmonary hypertension, and self assessment of overall health in the thrombolysis groups, this meta-analysis provides a convincing argument for the use of thrombolysis in submassive PE.
If I have a submassive PE, I want thrombolysis. (I am under 65 years). I would want half-standard dose as per the MOPETT trial. If my dad (he is over 65 years) had a sub-massive PE I would not recommend thrombolysis as the 12.9% chance of major bleeding means that the risks may outweigh the benefits.

Question 49

SEPSISPAM: High versus low Blood-Pressure Target in Patients with Septic Shock
NEJM. 2014;

Answer 49

Intervention - target MAP 80-85, for maximum of 5 days or until weaned from vasopressor support

Control - target MAP 65-70

The Bottom Line
For the majority of patients in septic shock a target MAP of 65-70 is a good starting point. However, in patients with chronic hypertension I will target a higher MAP. This is because, even though this did not improve mortality, it did reduce the need for renal replacement therapy with a NNT of 9.5. A number of studies have previously demonstrated that the need for renal replacement therapy is associated with mortality.
In patients without hypertension further studies comparing a MAP of 65 with a lower MAP of e.g. 55 would be beneficial

Question 50

BEST:TRIP: A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury
Chestnut. NEJM 2012

Answer 50

The Bottom Line
In patients with severe traumatic brain injury, care guided by ICP monitoring did not improve outcomes compared with management based on clinical and examination findings. Therefore I would not recommend the introduction of ICP monitoring in a resource limited setting. However, in countries such as the UK where ICP monitoring is already standard practice, I would not change practice based on this study as no harm was found, and there are significant differences in the health care provided between the UK and Bolivia/Ecuador.

Question 51

TracMAN JAMA 2013

Answer 51

The Bottom Line
This trial does not provide evidence supporting early tracheostomies performed around day 4 compared to day 10 (no evidence of difference).
Tracheostomy procedures are associated with a 6.3% incidence of complications requiring interventions, which must be weighed against any potential benefit.
Many commentators have interpreted this trial to mean there is no benefit from performing early tracheostomies (evidence of no difference), as many will not need it if we wait until day 10.
However, some patients need tracheostomies for good reasons (e.g. neurological disease) and they were not included in this study.

Question 52

Efect of Intensive vs. Moderate Alveolar Recruitment Strategies Added to
Lung-Protective Ventilation on Postoperative Pulmonary Complications. A
Randomised Clinical Trial. JAMA 2017

Answer 52

PEEP 13 vs 8

CTS patients
Higher PEEP group did better

Should we routinely use recruitment maneuvres as described in this trial to prevent post operative pulmonary complications?
Possibly. In contrast to the open lung strategy employed by the ART trial, a more
conservative approach was successfully used in this trial. Further data is required to
clarify the role of recruitment maneuvres in ventilatory management.

Question 53

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med
2017

Answer 53

a single-centre, randomised controlled trial comparing APRV against low tidalvolume
lung protective ventilation (LTV) in patients with ARDS conducted in the West
China Hospital of Sichuan University, China

Patients in the APRV group had signifcantly more VFDs by day 28 than those in the LTV
group

More patients receiving APRV were successfully extubated and fewer required tracheostomy

There was no difference in the incidence of pneumothorax; 3 vs. 7 in the APRV vs LTV groups, respectively (P = 0.199). Neuromuscular blockade, prone
positioning, nitric oxide or HFOV was required in 23 (34%) patients in the LTV arm and 6
(8%) receiving APRV. Length of stay was signifcantly reduced in ICU

Question 54

NUTRIREA-2 trial

Answer 54

Included more unwell patients than calories (had to be MV)

No differences EXCEPT;
provides new cautionary evidence against early enteral nutrition due to gastrointestinal complications. The rates of vomiting, diarrhoea and psuedo-obstruction were statistically higher, but most alarming was the four-fold increase in bowel ischaemia (5 patients in the parenteral group vs. 19 patients in the enteral group, P = 0.007)

Should we routinely choose initial parenteral rather than enteral nutrition in haemodynamically unstable critically ill patients?
Possibly. Although parenteral nutrition offers no survival beneft over enteral nutrition
in this setting, its use results in less gastrointestinal complications, a fnding seen in two
major randomised controlled trials

Question 55

CALORIES tria

Answer 55

n = 2,388 patients were randomised to parenteral (n = 1,191) or enteral (n = 1,197) nutrition, commenced within 36 hrs of ICU admission and continued for 5 days

Nutritional targets were set at 25 kcal/kg/day.
Neither group met nutritional targets.

Overall mortality was 33.1% in the parenteral group and 34.2% in the enteral group

Hypoglycemia was less frequent in the parental
nutrition group (3.7% vs. 6.2%; P = 0.006), as was vomiting (8.4% vs. 16.2%; P < 0.001).

There were no differences in infectious complications or other outcomes.

Question 56

Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial.
Lancet Respir Med 2017;5(3):180-190

Answer 56

Trial stopped early due to harm from both internvention

Hyperoxia has shown no beneft and may well be harmful. Hypertonic saline, as used, didn’t reduce overall fuid volumes and was predictably limited by hypernatraemia.

Question 57

Biomarker based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomised controlled trial. Intensive Care Med
2017;43:1668-1677

Answer 57

• guideline for empirical antifungal prescription stipulated patients had to be suffering a persistent fever, for greater than 48 hours, despite antibiotics and exhibit signs of haemodynamic instability in the last 12 hours, and also had to fulfl at least one major and two minor criteria, as outlined below;

Major Criteria - Systemic antibiotic therapy, Total parenteral nutrition
Minor Criteria - Central venous catheter, Dialysis, Major surgery, Pancreatitis. Use of corticosteroids

Intervention group had serum levels of (1,3)-ß-D-glucan,
mannan and anti-mannan antibody measured on day 0 and day 4

Significnatly more patients in intervention group had antifungals ceased
No increased cases of invasive candida

NB - very small study

Question 58

DEXILIRIUM

Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective
Noncardiac Surgery - A Randomized Clinical Trial. JAMA Surg

Answer 58

Pts >68 yo given intra op dexmed

No differnce in peri-operative delirium and post-operative cognitive dysfunction (POCD)

Question 59

DAWN NEJM 2018

Answer 59

Included if they had evidence of occlusion of the intracranial internal carotid artery, the frst section of the
middle cerebral artery, or both on CT angiography or MR angiography, and they had a mismatch between imaging and clinical severity of stroke, in addition to an absence of haemorrhage and a good premorbid level of function.

Outcomes -
For every 2 patients who underwent thrombectomy, 1 patient had less disability at 90 days compared with the control group. For every 2.8 patients who underwent
thrombectomy, 1 more had functional independence at 90 days than in the control
group

Question 60

TRIBE

Transfusion Requirement in Burn Care Evaluation – A Multicentre Randomised Prospective Trial of Blood Transfusion in Major Burn Injury. Ann Surg
2017;

Answer 60

examined whether a restrictive transfusion policy would reduce bloodstream infection (BSI), organ dysfunction and mortality in critically ill burns patients, within 96 hours of injury and suffering ≥ 20% total body surface area burns (TBSA)

randomised to either a restrictive (target haemoglobin, Hb, 70 – 80 g/L) or a liberal transfusion strategy (target Hb 100 – 110 g/L) for the duration of their hospital
admission

No differences between groups