Syllabi - Critical Care - Therapy Scenario (Alternative 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.

Read the article and decide:

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]

95% Confidence Interval (CI) on an NNT = 1 / (limits on the CI of its ARR)
= +-1.96 sqrt(((CERx(1-CER))/(# of control pts.)) + ((EERx(1-EER))/(# of exper. pts.)))
= +-1.96 sqrt(((0.096x0.904)/730) + ((0.028x0.972)/711))
= ±2.4%

Your Calculations:

		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?

Do these results apply to your patient?

Is your patient so different from those in the trial that its results can't help you? :No

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

Method I: f

Risk of the outcome in your patient, relative to patients in the trial. expressed as a decimal: 1.0

NNT/F
= ________
= 22 (but note confidence interval included infinity)
(NNT for patients like yours)
Method II: (PEER x RRR)

Your patient's expected event rate if they received the control treatment:

PEER:______
1 / (PEER x RRR)
= 1/________
= __________

(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

Additional Notes

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

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]

Comments

Study terminated early because of decrease in enrollment to below 20% of predicted values
Study powered to detect a 5.5 % decrease in mortality or greater so can not comment whether transfusion is associated with a smaller decrease in mortality. Since the outcome is mortality, any decrease in mortality may be clinically important
Those patients who were not enrolled were slightly older, had similar APACHE scores and co-morbid diagnoses except for cardiac disease possibly limiting the generalizability of the results.
Study had inadequate power to state whether these results apply to patients with significant coronary disease.
Subgroup analysis suggests that restrictive transfusion may be associated with reduced 30 day mortality in patients less than 55 years of age (5.7% restrictive group and 13% in the liberal transfusion group) and in patients with APACHE II scores less than 20 (8.7% restrictive group and 16.1% liberal group).