### Therapy Scenario

A 55 year old male is admitted to the ICU from the operating room after having debridement of infected pancreatic necrosis. His past medical history is significant for alcohol consumption (6 beers per day) and a 50 pack year history of tobacco use. His postoperative orders include sucralfate. You explain that a recent clinical trial suggests that the risk of upper gastrointestinal bleeding is lower with the use of ranitidine. The surgeon states that he prefers sucralfate and would like to see the evidence. You formulate the question, “in mechanically ventilated patients who have undergone gastrointestinal surgery, do H2 blockers reduce the risk of upper gastrointestinal bleeding compared to the use of sucralfate?”

You search Best Evidence that you loaded on the computer in the ICU, using the terms ‘Upper GI bleeding’ and ‘H2 blockers’ and find the randomized clinical trial that assesses the risk of upper gastrointestinal bleeding in mechanically ventilated patients receiving sucralfate compared to ranitidine. The abstract appears to be exactly what you are looking for and the design is a randomized trial so you go to the library to pull the article (NEJM 1998;338:791-7). You read the article and see the surgeon on rounds the next morning and tell him you would like to discuss the evidence for your question.

• 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

#### Citation

Cook D, Guyatt G, Marshall J, et al.
A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. NEJM 1998;338:791-7

#### 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?
Yes
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
$$9.6%$$ $$2.8%$$ $$(9.6%-2.8%)/9.6%$$
$$= 71%$$
$$9.6% – 2.8%$$
$$= 6.8%$$
$$[4.3% times{to} 9.3%]$$
$$1/6.8%$$
$$=~15~times{pt}s$$
$$[11 ~ text{to} ~ 23]$$

begin{align}
95% text{Confidence Interval (CI) on an NNT} &= 1 / (text{limits on the CI of its ARR})\
&= pm 1.96sqrt{frac{text{CER}times(1-text{CER})}{text{# of control pts.}}+frac{text{EER}times(1-text{EER})}{text{# of exper. pts.}}}\
&= pi 1.96 sqrt{frac{0.096times 0.904}{730} + frac{0.028times0.972}{711}} = ±2.4% \
&= pm2.4%
end{align}

Relative Risk Reduction (RRR) Absolute Risk Reduction (ARR) Number Needed to Treat (NNT)
CER
Sucralfate
EER
Ranitidine
(CER – EER)/CER CER-EER 1/ARR
$$3.8%$$ $$1.7%$$ $$(3.8% – 1.7%)/3.8%$$
$$= 55%$$
$$3.8% – 1.7%$$
$$= ~ 2.1%$$
$$[4.0% – 0.3%]$$
$$1/2.1%$$
$$= ~ 47 ~ pts$$
$$[25 ~ to ~ 333]$$

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

##### Do these results apply to your patient?

1. No, study included mechanically ventilated surgery patients

##### How great would the potential benefit of therapy actually be for your individual patient?
1. Method I: f
begin{align}
text{Risk of the outcome in your patient,}\\ text{relative to patients in the trial. expressed as a decimal: 1.0}\\
text{NNT/F}\\
&= 47/1 \\
&= 47\\
text{(NNT for patients like yours)}
end{align}

2. Method II: 1 / (PEER x RRR)
begin{align}
text{PEER:} \\
1/(text{PEER}timestext{RRR}) \\
&=1/\_\_\_\_ \\
&=\_\_\_\_\_ \\
text{(NNT for patients like yours)}
end{align}

##### 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

• This study also found that the risk of ventilator associated pneumonia, a purported risk with the use of ranitidine, was no different in the groups that received ranitidine compared to the group that received sucralfate.

### UGI Bleed: Ranitidine reduces the risk compared to sucralfate

#### Clinical Bottom Line

• In mechanically ventilated patients, the use of ranitidine compared with sucralfate reduces the risk of upper gastrointestinal bleeding.

#### Citation

Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. NEJM 1998;338:791-7

#### Clinical Question

In mechanically ventilated patients, does the use of ranitidine compared to sucralfate reduce the risk of upper gastrointestinal bleeding.

#### Search Terms

Upper gastrointestinal bleed and ranitidine

#### The Study

• Double-blinded, concealed randomisation, controlled trial with intention to treat analysis. Mechanically ventilated medical and surgical patients.
• Control group (Sucralfate) N= 604, 604 analysed. Control group received ranitidine placebo. Neither group had Gastric pH checked.
• Experimental group (Ranitidine) N= 596, 596 analysed. Experimental group received sucralfate placebo.

#### The Evidence

Outcome Time to Outcome CER EER RRR ARR NNT
UGI bleed In hospital $$3.8%$$ $$1.7%$$ $$55%$$ $$2.1%$$ $$47$$
$$95%text{ CI}$$ $$78% – 8%$$ $$4% – 0.3%$$ $$25 – 333$$
Vent associate Pneumonia In hospital $$16.2%$$ $$19.1%$$ $$18%text{ increase}$$ $$2.9%text{ increase}$$ $$34 ~ additional ~ pneumonias$$
$$95% CI$$ $$8% decrease to 51% increase$$ $$1.4% ~ decrease ~ to ~ 7.2% ~ increase$$ $$text{72 ~ fewer ~ to ~ 14 ~ additional}$$