Evidence Base

Question 1

Summary of IRONMAN trial (2016) - iron infusion in ICU

Answer 1

Question:
In anaemic critically ill patients, does early administration of IV iron c/w placebo reduce the requirement for blood transfusion?

Design / Setting:
RCT in Perth, WA
Patients with severe sepsis excluded.

Intervention: IV iron - 1g total

Outcome:
IV iron did not result in a reduction in red blood cell transfusion compared to placebo, however they did leave hospital with a higher haemoglobin level.

Question 2

Summary of TRISS trial (2014) - transfusion in septic shock

Answer 2

Question: In patients with septic shock does lower or higher transfusion target improve mortality

Design: RCT

Population: adults in ICU with septic shock + Hb < 90

Intervention: transfusion threshold < 90
Control: transfusion threshold < 70

Outcome: mortality @ 90/7. There was no difference in mortality between liberal and restrictive transfusion strategies.

Question 3

Summary of CRASH-2 Trial Lancet (2010): TXA in trauma

Answer 3

Question: In trauma patients with haemorrhage or at r/o haeomrhage does early administration of TXA affect mortality / incidence of occlusive events and rate of blood transfusion?

Design: International RCT >20,000

Population: adults with trauma

Intervention: 1g of TXA within the first 3 hrs, followed by 1g over the following 8 hours

Control: placebo

Outcome: Mortality @ 30/7. Mortality improvement was small but reached significance because of the massive number of enrolled patients.

Question 4

Summary of CRASH 3 trial (2019): TXA in TBI

Answer 4

Question: In patients with traumatic brain injury (TBI), does the administration of tranexamic acid (TXA) under 3 hours from injury, compared with placebo, reduce head injury associated in-hospital mortality within 28 days?

Design: International RCT

Population: Adults with TBI GCS < 12 or ICH on CTB

Intervention: 1g over 10 minutes followed by IV infusion of 1g over 8 hours
Control: placebo

Outcome: 28/7 in hospital mortality
Conclusion:
* When given with 3 hours of the injury, the mortality from mild-moderate TBI was reduced ( non-significantly)
* With low r/o harm should advocate for TXA administration within 3 hours of TBI

Question 5

Summary of TRANSFUSE study (2017) (Age of PRBC and effects on outcome)

Answer 5

Large international RCT looking at transfusion of fresh vs older PRBC in critically ill patients. Target was Hb >70

This study confirms that there is no benefit gained from using the freshest blood available in the blood bank for transfusing critically ill patients. Conversely it also confirms that there is no harm from using the oldest blood in the blood bank to transfuse critically ill patients

Question 6

Give a brief overview if the surviving sepsis campaign and latest guidelines

Answer 6

Overview and rationale:

* The Surviving Sepsis Campaign (SSC) is a joint collaboration of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) 
* Developed to reduce mortality and morbidity from sepsis worldwide. 
* Predominantly apply to high resource settings
* Not widely endorsed by ANZICS and not used in Australia and New Zealand.

First guidelines = 2004
Newest SSC guidelines = 2021

* Recognise new SEPSIS 3 definition, total > 90 recommendations
* They recommend against using q SOFA c/w SIRS, NEWS OR MEWS as a single screening tool for sepsis /septic shock -> strong recommendation, mod-quality evidence
* Downgraded evidence from strong -> weak for prior recommendation for up to 30ml/kg crystalloid fluid resuscitation
* They suggest for adults with sepsis induced hypoxic resp failure - HF02 over NIV - weak recommendation They DON’T recommend IV Vit C

Question 7

What is Early Goal Directed Therapy ( EGDT) in sepsis. List the relevant trials

Answer 7

Definition:
EGDT is a protocolised approach to early ( within 6 hours) targeted management of specific haemodynamic goals with early interventions e.g. antibiotics, fluids, vasopressors, inotropes and blood.

5 Early Goals
-CVP 8-12mmHG
-MAP>65mmHg
-U/O >0.5ml/kg/hour
-Scv02 > 70%
Hct > 0.3

Rationale:
Septic patients at risk of septic shock
Septic shock incorporates MOF - poor O2 delivery to tissues
Early optimisation of O2 delivery to tissues improves outcome

Evidence:

Rivers trial 2001
P - Single centre american trial ~ 250 patients with sepsis / septic shock
I - protocol including EGDT targets
C - usual care
O - Significant benefit of EGDT in survival

Significant limitations -> single centre, non blinded, noted conflict of interests e.g. lead author associated with ScVO2 measuring CVC

3 subsequent NEJM trials give body of evidence that says EGDT is non superior to usual sepsis care :

Process trial - 2014 US
**ARISE trial **- 2014 Aus/Nz
Promise trial - 2015 UK

P - multi-centres, randomised trials. Adults with suspected sepsis
I - EGDT for 6 hours based on Rivers study
C - Usual care
O - No differnce in mortality

These three landmark trials show that there was no difference in mortality between EGDT and usual care, which often included use of CVC and MAP targets anyway, but didn’t involve use of continuous monitoring of ScV02 or CVP to guide management. Multicentre, international evidence presented in robust randomised trials