Evidence summaries: RBC transfusion triggers

✓ Acute interventions – intensive care (7 PICO’s) (Cécile Aubron & Jerrold Levy)

✓ Critically ill intensive care patients✓ Septic shock✓ Orthopaedic and (non-)cardiac surgery✓ Cardiac surgery✓ Coronary heart disease✓ Acute gastrointestinal bleeding✓ Acute bleeding

✓ Haematology & Oncology (2 PICO’s) (Richard Gammon)✓ Neurology (2 PICO’s) (Cynthia So-Osman)

✓ Acute CNS injury✓ Cerebral perfusion disorders

Thank you to the presenters!

PICO questions

Should more restrictive RBC transfusion triggers (Intervention) versus more liberalRBC transfusion triggers (Comparison) be used in- Critically ill, but clinically stable intensive care patients (adults)? (Population 1)- Adult patients with septic shock? (Population 2) (COMBINED)

- Adult patients with orthopaedic and non-cardiac surgery? (Population 3)- Adult patients with coronary heart disease? (Population 4)- Adult patients with cardiac surgery? (Population 5)

- Adult patients with acute (gastrointestinal) bleeding? (Population 6/7)

- Adult patients with haematological diseases? (Population 8)- Adult patients with solid tumours? (Population 9)

- Adult patients with acute central nervous system injury? (Population 10)- Adult patients with cerebral perfusion disorders? (Population 11)

Outcomes of interest: clinical outcomes: mortality, morbidity-related outcomes that occured during hospitalisation, RBC utilisation

For each PICO:

• 30-day mortality as a critical outcome

• Draft recommendation

• Justification

• Relevant panel discussion points

• Audience vote on proposed recommendation

CRITERIA JUDGEMENTRESEARCH

EVIDENCEADDITIONAL CONSIDERATIONS

1. DESIRABLE EFFECTSHow substantial are the desirable anticipated

effects?

2. UNDESIRABLE

EFFECTS

How substantial are the undesirable

anticipated effects?

3. CERTAINTY OF

EVIDENCE

What is the overall quality of the evidence of

effects?

4 (5). VALUES

Is there important uncertainty about or

variability in how much people value the

critical outcomes?

5. BALANCE OF

EFFECTS

Does the balance between desirable and

undesirable effects favor the intervention or

the comparison?

6. RESOURCES

REQUIRED

How large are the resource requirements

(costs)?

7. COST

EFFECTIVENESS

Does the cost-effectiveness of the intervention

favor the intervention or the comparison?

8. EQUITY What would be the impact on health equity?

9. ACCEPTABILITYIs the intervention acceptable to key

stakeholders?

10. FEASIBILITY Is the intervention feasible to implement?

Evidence-to-Decision framework

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Haematology and oncology Should more restrictive RBC transfusion triggers (Intervention) versus

more liberal RBC transfusion triggers (Comparison) be used in

- Adult patients with haematological diseases? (Population 8)

- Adult patients with solid tumours? (Population 9)

HaematologyCRITICAL OUTCOME: 30-day mortality

Haematology (PICO 10)

No Hb trigger recommendation

Plus: The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger in haematology patients (including non-malignant conditions) (Y/N)

Justification: Insufficient evidence (two pilot studies in acute leukaemia, total 149 patients). No signal for undesirable effects.

Notes: Hb trigger in the two included trials was 7-8g/dL

Oncology (PICO 11)

No recommendation for Hb trigger (Y/N)

The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger in oncology patients (Y/N)

Justification: No evidence

Notes: Only available study was in post-op surgical oncology setting in ICU – considered in surgical (PICO 5)

CNS injury

Should more restrictive RBC transfusion triggers (Intervention)versus more liberal RBC transfusion triggers (Comparison) be

used in adult patients with acute central nervous system injury? (Population 10)

McIntyre et al (2006)

CRITICAL OUTCOME: 30-day mortality

Central nervous system injury (PICO 12)

No Hb trigger recommendation (Y/N)

Plus: The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger in patients with CNS injury (Y/N)

Justification: Very low level of evidence for all outcomes

Notes: Post hoc analysis of TRICC study (67 patients, randomised to Hb trigger of 7 or 10g/dL). No undesirable effects observed

Cerebral perfusion disorders

Should more restrictive RBC transfusion triggers (Intervention)versus more liberal RBC transfusion triggers (Comparison) be

used in adult patients with cerebral perfusion disorders? (Population 11)

Naidech et al (2010)No mortality data available CRITICAL OUTCOME: any adverse event related to transfusion

CRITICAL OUTCOME: pulmonary edema or respiratory distress

Cerebral perfusion disorders (PICO 13)

Recommendations: No Hb trigger recommendation (Y/N)The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger in patients with cerebral perfusion disorders (Y/N)

Justification: No evidence for any outcomes related to restrictive transfusion strategy because participants randomised to Hb trigger of 10 or 11.5 g/dL. Not considered a restrictive strategy.

Notes: One study of 44 patients with subarachnoid haemorrhage No undesirable effects observed.

Coronary heart diseaseShould more restrictive RBC transfusion triggers (Intervention) versus more liberal RBC transfusion triggers (Comparison) be used in adult

patients with coronary heart disease? (Population 4)

Coronary heart disease CRITICAL OUTCOME: 30-day mortality

CRITICAL OUTCOME: myocardial infarction

Coronary heart disease (PICO 7)

Recommendation: The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger in patients with acute coronary syndromes (Y/N)

Justification: There is an overall low level of evidence, and concern regarding undesirable effects with a restrictive strategy

Note: A conditional recommendation for either strategy cannot be made because of the concern over the possibility for undesirable effects in the restrictive group

Critical care

Should more restrictive RBC transfusion triggers (Intervention) versus more liberal RBC transfusion triggers (Comparison) be

used in adult critically ill, but clinically stable intensive care patients? (Population 1) including adult patients with septic

shock? (Population 2)

Critically ill and septic shockCRITICAL OUTCOME: 30-DAY MORTALITY

Critical care (PICO 4)

Strong recommendation (Y/N)• The ICC-PBM guideline panel recommends a transfusion trigger of 7 g/dL for treatment of anaemia in

critically ill patients who are not actively bleeding. (strong recommendation, moderate certainty)• This recommendation may not apply to patients with acute coronary syndromes and CNS injury/cerebral

perfusion disorders.• The ICC-PBM guideline panel suggests further research in these areas.

Justification: No evidence of increased mortality or other undesirable effects, and substantial reduction in red cell exposure and utilisation.

Notes: • Critical care population highly heterogeneous (reason for qualification)• Includes septic shock (originally separate PICO question 8)• Hb 7g/dL trigger represents the value used in the included trials• Panel had extensive discussion on whether the “may not apply” should include patients with a history of

coronary artery disease/other cardiovascular disease

Cardiac surgery

Should more restrictive RBC transfusion triggers (Intervention)versus more liberal RBC transfusion triggers (Comparison) be

used in adult patients undergoing cardiac surgery? (Population 5)

Cardiac surgery

CRITICAL OUTCOME: 30-day mortality

Strong recommendation:The ICC-PBM guideline panel recommends using a transfusion trigger of Hb <7.5 g/dL in cardiac surgery patients, based on moderate certainty in the evidence of effects. (Y/N)

(Strong recommendation, moderate level of evidence)

Justification: No evidence of increased mortality or other undesirable effects, and substantial reduction in red cell exposure and utilisation.

Note: 7.5g/dL trigger represents the value used in the included trials

Cardiac surgery (PICO 9)

Orthopaedic surgeryShould more restrictive RBC transfusion triggers (Intervention) versus more liberal RBC transfusion triggers (Comparison) be used in adult

patients undergoing orthopaedic surgery? (Population 3)

Orthopaedic surgeryCRITICAL OUTCOME: 30-day mortality

CRITICAL OUTCOME: myocardial infarction

Orthopaedic surgery (PICO 5)

Conditional recommendation (Y/N)The ICC-PBM guideline panel suggest using a transfusion trigger (Hb <8 g/dL) in elderly patients with hip fracture

(weak recommendation, moderate evidence)

Justification: No effect on mortality (although wide CI) or functional outcomes (walk independently at 60days). However, uncertainty regarding undesirable effects, in particular AMI. Therefore weak recommendation.

Notes: • Hb 8g/dL trigger represents the value used in the included trials• Can we extrapolate trial data in hip fracture to elderly patients undergoing

other orthopaedic surgery? And all patients undergoing other orthopaedic surgery? And other non-ortho, non-cardiac surgery?

• Major evidence gaps in these areas - research recommendation to be made

Other surgery

Non-orthopaedic & non-cardiac surgery

CRITICAL OUTCOME: 30-day mortality

Note: vascular surgery not discussed by panel due to insufficient time

Other surgery (non-ortho, non-cardiac, PICO 5 cont’d)

Recommendation: The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger in other surgical populations (Y/N)

Justification: There is an overall low level of evidence, and concern in surgical oncology patient regarding undesirable effects with a restrictive strategy

Note: A conditional recommendation for either strategy cannot be made because of the concern over the possibility for undesirable effects in the restrictive group

Acute upper GI bleedingShould more restrictive RBC transfusion triggers

(Intervention) versus more liberal RBC transfusion triggers (Comparison) be used in adult patients with acute (gastrointestinal) bleeding? (Population 6/7)

Acute (gastrointestinal) bleeding

CRITICAL OUTCOME: 30-DAY MORTALITY

Acute GI bleeding (PICO 6)

Conditional recommendation (Y/N): The ICC-PBM guideline panel suggest transfusion trigger of Hb 7-8g/dL in patients with acute upper GI bleeding who are haemodynamically stable (or “who are not exsanguinating”?)(weak recommendation, low level of evidence)

The ICC-PBM guideline panel decided to formulate a recommendation for further research on the use of restrictive transfusion trigger acute GI bleeding (Y/N)

Justification: Two trials, both excluded exsanguinating patients. Lower mortality with restrictive strategy. No evidence of undesirable effects. Reduction in RBC exposure and utilisation. Notes: • PICO was “acute GI bleeding”. Recommendations limited to acute upper GI bleeding.• “Massive exsanguinating” patients excluded from the trials. No trials identified in

lower GI bleeding.• Guidelines should emphasise that in the acutely bleeding patient, Hb is not the

deciding factor for transfusion.• Trials used Hb triggers (e.g. Hb 7) to achieve specified Hb target ranges (e.g. Hb 7-9).

Acute bleeding (PICO 14)No recommendation for Hb trigger

The ICC-PBM guideline panel does not recommend research on the use of Hb triggers for transfusion in patients with major bleeding (exsanguinating patients) (Y/N)

Justification: No evidence. One pseudo-randomised trial from 1956 identified.

Notes: • Panel view is that a Hb concentration alone should not be used to determine

the need for transfusion in an acutely bleeding (i.e. major haemorrhage) scenario. Recommend refer to existing massive transfusion/major haemorrhage protocols/guidelines)

• ICC PBM Guidelines should emphasise that in the acutely bleeding patient, Hb is not the deciding factor for transfusion.

Question and discussion