Education News and Reviews

Read our latest blog articles and Journal Club reviews, catch up on our Quants or post your own article

Latest education news from CCCEG

Quisque eleifend elit a mauris malesuada rutrum. Quisque fermentum nibh in libero gravida auctor.

Presented by Capt (MD) Dimitrios Sidiras HAF

STUDY QUESTION:

In patients undergoing cardiac surgery, who have a moderate-to-high risk of death, is a restrictive transfusion strategy (trigger = 75 g/L) non-inferior to a liberal strategy (Trigger = 95 g/L intraoperatively/ICU or 85 g/L on the ward) with respect to a composite outcome of death, myocardial infarction, stroke and acute kidney injury requiring dialysis at 6 months after surgery?

HOW DOES THIS RELATE TO OUR PRACTICE ON NCCU?

The most common situation leading to massive transfusion is cardiac surgery, but trauma, where physical injury and blood loss combine, remains the best-studied example and trauma patients are the other large group of patients consuming large amounts of red cells.

We currently follow the NICE guidelines for red blood cells transfusion which sets a threshold of 70 g/L and a hemoglobin concentration target of 70–90 g/L after transfusion (for patients with acute coronary syndrome, the trigger is 80 g/L and the hemoglobin concentration target is 80–100 g/L after transfusion). Our local TBI protocol sets a threshold of 90 g/L. This does not apply to major haemorrhage, history of acute coronary syndrome or chronic anaemia.

Trauma patients in need of the major haemorrhage protocol are transfused in the Emergency Department, aiming for a haemoglobin concentration target above 80 g/L. However the suspicion of major haemorrhage is not based on haemoglobin concentration, but instead on the mechanism of injury and the vital signs.

WHAT DO WE CURRENTLY KNOW ABOUT THIS AREA?

At present most centres are using the 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery (or something very close to that). In addition, we need to find a balance between optimal patient care and the appropriate use of a limited resource.

The two approaches to blood transfusion currently are:

  • The restrictive approach, which is based on limiting the infectious and non infectious (TRALI, pulmonary oedema, multiorgan system dysfunction etc.) risks of transfusion
  • The liberal approach, which is based on the fact that patients who are at high perioperative risk may be more susceptible to anaemia-induced tissue hypoxia

When it comes to the brain…..the evidence is conflicting!

There is clear clinical and guideline agreement that Hb less than 70 g/L in critically ill patients with TBI requires red blood cell transfusion (RBCT). However, the exact threshold between 70 and 100 g/L remains a contentious issue. Recent data from a randomized controlled trial (RCT) and meta-analysis found no difference in neurological outcome between the restrictive and liberal transfusion strategies, but the overall quality of the evidence was low. Several observational studies have shown an association between anemia and poor outcomes in patients with TBI. However, other studies evaluating anemia and TBI outcomes have not demonstrated a consistent risk of harm (see further reading section).

Additionally, several studies have shown that RBCT administration in TBI is associated with increased mortality, decreased functional outcomes, increased ICU length of stay, and impaired cerebral autoregulation. A liberal transfusion strategy applying a threshold trigger of 100 g/l was associated with an increased risk of progressive cerebral hemorrhagic injury and thromboembolic events. However, evidence from other observational studies in patients with TBI is conflicting, with data to support a lack of association between RBCT administration and worse outcome in TBI.

WHY WAS THIS STUDY NEEDED?

Patients undergoing cardiac surgery often have significant transfusion requirements and there is wide variation in transfusion practices among clinicians and institutions. Robust evidence has emerged in other patient populations (general critical illness, septic shock, etc) that a restrictive transfusion strategy is at least as good as (and possibly better than) a liberal one. If a restrictive strategy is shown to be noninferior to a liberal one, and this can influence practice, there is the potential for significant cost savings and decreased use of a scarce and limited resource.

AT JOURNAL CLUB WE SHOULD DISCUSS THE FOLLOWING:

  • Should we compare transfusion practices in cardiac surgery with those in trauma and TBI?
  • Transfusion thresholds for trauma and TBI. We aim for higher than other critically ill groups. Why? Do latest studies agree with that?
  • This study is unusual in that it is about patients at a higher risk of death and other complications than some of the other studies.
  • It also shows that a RCT overturned TITRe2
  • It focuses on transfusion of red blood cells only
  • No data exists for transfusion and TBI. How would data like CENTER-TBI answer this question in TBI?
  • How often do we ignore guidelines and stick to personal experience or instincts?

SHOULD WE CHANGE PRACTICE ON NCCU

We are already following a rather restrictive strategy when it comes to transfusing red blood cells, so we are probably going to the right direction according to this study. Furthermore, we base our practice on a multivariable approach that includes fluid resuscitation and coagulopathy.

Maybe we should wait for the next big “transfusion in trauma” or “transfusion in TBI”  study focusing on non-inferiority of restrictive transfusion strategy and then check how cost/effective is our practice. In any case, excessive concern about cost-effectiveness shouldn’t change our approach to cases where we highly suspect major haemorrhage: We should have a low threshold for transfusion.

FURTHER READING

The Bottom Line

Hematology Times

EuroSCORE I

Transfusion practices in traumatic brain injury

Variation in blood transfusion and coagulation management in TBI at the ICU

RBCT in Patients With TBI: A Systematic Review and Meta-Analysis


 

Presented by Dr Luke Terrett

 

Study Question:

In adults with TBI and ICP > 20 mmHg, despite “stage 1 treatments,” does hypothermia (32°C – 35°C) improve outcome compared with standard care?

How does this relate to our practice on NCCU?

Traumatic Brain Injury is almost the raison d’être of NCCU.

Elevated ICP is a frequent finding that requires prompt management in order to prevent further brain injury.

Therapeutic hypothermia (TH) has been shown to lower ICP and is a central part of our protocolised management of patients with TBI and elevated ICP.

TH has been shown to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest. The original 2 studies (HACA and Bernard) from 2002 targeted 32-34°C but in a more recent study (TTM trial), 36°C has been shown to be as good as 33°C. Different population and different indication.

Frankly, removing TH would go against our almost religious approach to the management of TBI – perhaps that is the reason why this study sits so uncomfortably. But, in our business, our thoughts should always be discordant and our actions should always make us uncomfortable. For this reason it is one of the most important studies in the context of how manage patients in Cambridge.

What do we currently know about this area?

TH may have a range synergistic neuroprotective effects:

  • It lowers the cerebral metabolic rate
  • Decreases excitotoxic neurotransmitter release
  • Decreases free radical formation
  • Decreases sustained electrical depolarisations
  • Inhibits proinflammatory and apoptotic pathways

TH lowers ICP perhaps through the following mechanisms, but we really don’t know:

  • Decreased inflammation
  • Decreased vasogenic edema
  • Decreased cerebral blood volume

However, TH is not without risks:

  • Coagulopathy/platelet dysfunction
  • Immunosuppression
  • Cardiac dysrhythmias
  • Hypotension
  • Pneumonia
  • Insulin resistance
  • Cold diuresis and electrolyte depletion
  • Decreased catecholamine responsiveness

Have a look at  Nature Reviews Neurology this blog.

Why was this study needed?

In the setting of TBI, multiple older studies showed mixed results. A 2014 systematic review and meta-analysis found possible benefit for therapeutic hypothermia in TBI. A well-designed RCT was needed to definitively answer the question.

At journal club we should discuss the following:

  • Hypothermia was applied quite early (after 5 min of sustained ICP > 20), seems a bit quick, see our letter.
  • Initial interventions were modest, yet safe, where does the risk of TH sit with this?
  • The study did not use other stage 2 treatments in hypothermia group unless persistent ICP elevation
  • What about how TH was achieved, it was quickly down to the target range 32-35°C, why not use an incremental, stepwise approach and achieve the minimum temp decrease required to control ICP?
  • What about all that fluid?
  • Sadly the trial stopped early after 387/600 patients enrolled, is this a problem?

 


Should we change practice on NCCU

Not based on the results of this study. They applied therapeutic hypothermia very differently than we do in the NCCU at Cambridge: They used it very early and prior to basic interventions, such as osmotherapy. Although basic is a word we use when we don’t know the harm a treatment really casues.

A trial that more closely mirrors our pattern of practice is needed prior to considering a change.

The next big RCT on TH in TBI, POLAR, has just finished enrolling patients, will this help us? Let’s see at journal club.


 

Further Reading

BTF guidelines

The Bottom Line 

Nature Reviews Neurology – Hypothermia for acute brain injury

https://www.nature.com/articles/nrneurol.2012.21

SNACC Review