### Alternate Therapy Scenario

You are attending in the ICU and are taking care of a 75 year old woman admitted with pneumonia, and requiring ventilatory support. You approach her husband to obtain consent for a blood transfusion. Her Hgb is 8g/dL. She has not had a transfusion in the past. You suggest that she would benefit from having a Hgb greater than 10 g/dl. He is a retired physician and clinical epidemiologist and asks if there is evidence to support having Hgb greater than 10 g/dl. You formulate the question, “In patients who are critically ill, does transfusion to a Hgb of at least 10 g/dL reduce mortality?”

You start up Medline enter “transfusion” and “critical illness” and you find the abstract and commentary for the multicenter, randomized controlled trial assessing transfusion requirements in critical care settings. The abstract looks helpful so you decide to go to the library and copy the original article NEJM 1999;340:409-17. You return to the ICU waiting area to discuss your findings with the patient’s husband.

• Is the evidence from this randomized trial valid?
• If valid, is the evidence important?
• If valid and important, can you apply this evidence in caring for your patient?

### Completed Therapy Worksheet for Critical Care Medicine

#### Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments randomised? And was the randomisation list concealed?
Yes
Were all patients who entered the trial accounted for at its conclusion? And were they analysed in the groups to which they were randomised?
Yes
Were patients and clinicians kept “blind” to which treatment was being received?
No
Aside from the experimental treatment, were the groups treated equally?
Yes
Were the groups similar at the start of the trial?
Yes

#### Are the valid results of this randomised trial important?

##### Sample Calculations
Occurrence of diabetic neuropathy Relative Risk Reduction (RRR) Absolute Risk Reduction (ARR) Number Needed to Treat (NNT)
Usual Insulin
Control Event Rate (CER)
Intensive Insulin
Experimental Event Rate (EER)
(CER – EER)/CER CER-EER 1/ARR
9.6% 2.8% (9.6%-2.8%)/9.6%
= 71%
9.6% – 2.8%
= 6.8%
[4.3% to 9.3%]
1/6.8%
= 15 pts
[11 to 23]

$$text{95% Confidence Interval (CI) on an NNT} = 1 / text{(limits on the CI of its ARR)}\ = pm 1.96 sqrt{frac{mathit{CER}times(1-mathit{CER})}{text{# of control pts.}} + frac{mathit{EER} times (1-mathit{EER})} {text{# of exper. pts.}}}\ = pm 1.96 sqrt{frac{0.096times0.904}{730} + frac{0.028times0.972}{711}} = pm2.4% \ = pm 2.4%$$

Relative Risk Reduction (RRR) Absolute Risk Reduction (ARR)
[95% CI]
Number Needed to Treat (NNT)
[95% CI]
CER EER (CER – EER)/CER CER-EER 1/ARR
23.3% 18.7% (23.3% – 18.7%)/23.3%
= 19.7%
4.6%
[-0.8% – 10.2%]
22
[NNT 10 to infinity, NNH 110 to infinity]

#### Can you apply this valid, important evidence about a treatment in caring for your patient?

:No

##### How great would the potential benefit of therapy actually be for your individual patient?

$$1.text{Method I:} f\ quad text{Risk of the outcome in your patient,}\ quad text{relative to patients in the trial. expressed as a decimal: } 1.0\ quad mathit{NNT}/mathit{F}\ quad = ______ \ quad = 22 text{ (but note confidence interval included infinity)} \ quad text{(NNT for patients like yours)}$$

$$2.text{ Method II:}\ quad 1 / (mathit{PEER}timesmathit{RRR})\ quad text{Your patient’s expected event rate if they received the control treatment:} \ quad mathit{PEER}:______ \ quad 1 / (mathit{PEER} times mathit{RRR}) \ quad = 1/___ \ quad = ___ \ quad text{(NNT for patients like yours)}$$

##### Are your patient’s values and preferences satisfied by the regimen and its consequences?
Do your patient and you have a clear assessment of their values and preferences?
Needs to be assessed in each patient
Are they met by this regimen and its consequences?
Needs to be assessed in each patient

The study was an equivalence study designed to detect an absolute difference in mortality of 5.5% between the treatment and control groups. Therefore, we can say that liberal transfusion is not associated with a 5.5% difference in mortality but can not comment on if there is a smaller treatment effect. Although the study was under powered to detect treatment effects less than 5.5%, a treatment effect less than 5.5% may be clinically meaningful since the outcome is mortality.

### Transfusion: In critically ill patients may not decrease mortality

#### Clinical Bottom Line

In critically ill patients, the liberal use of blood transfusions (Hgb 10 g/dl) is not associated with a 5.5% or greater reduction in 30 day mortality.

#### Citation

A multicenter, randomized, controlled clinical of transfusion requirements in Critical Care NEJM 1999;340:409-17

#### Clinical Question

In a critically ill patient, will restrictive blood transfusion practices be equivalent to liberal transfusion practices

#### Search Terms

“transfusion” and “critical care” and “death”

#### The Study

• Concealed, unmasked, randomized, controlled clinical trial of equivalency with intention-to-treat analysis. Patients >16 years of age admitted to ICU with <9.0g/dL. Powered to detect a 5.5% or greater decease in 30 day motality.
• Control Group (Liberal strategy of transfusion): (N=420, 416 analyzed); Transfuse to Hgb 10-12 g/dL
• Experimental Group (Restrictive strategy of transfusion): (N=418, 413 analyzed); Transfuse to Hgb 7-9 g/dL.

#### The Evidence

Outcome Time CER EER RRR ARR [95% CI] NNT [95% CI]
Death 30 day 23% 19% 20% 4.6% [-0.8% – 10.2%] 22 [NNT 10 to infinity, NNH 35 to infinity]
60 day 26% 23% 14% 3.8% [-2.1% – 9.5%] 33 [NNT 11 to infinity, NNH 35 to infinity]