Stress Ulcer Prophylaxis in ICU

!  Toshio Fukuoka MD
!  Cardiovascular Surgery, Emergency Department
!  and Vice Director of ICU

!  Nagoya National Hospital
!  Nagoya, JAPAN

Nov. 16 2003 Joint Congress of KSCCM & JSICM in Seoul

!  Scenario and Questions

Joint Congress of KSCCM & JSICM in
Nov. 16 2003
Seoul

" You are a patient of disease A. You are
admitted to the hospital and the standard
treatment started. It will take a week.
" Disease A has a clinically significant
complication. It may cause a surgery or
transfusion or prolongation of hospital stay.
" Drug X prevents the complication partially.
" You and the doctor start to discuss about
adding the drug to your treatment.

" The doctor tells your risk of the complication
in probability, and the treatment effect of
Drug X in risk ratio (RR) to you.
" In this case, risk ratio (RR) is the proportion
of the probability of the complication with
Drug X to without it.
" If Drug X has no effect, RR is “1”. If Drug X
halves the risk, RR is “0.5”.


" Please write down your threshold RR for
taking Drug X for each case.
" If you will not take the drug, your threshold
RR is “0”. “0.5” in the threshold RR means
that you will take Drug X when it reduce the
risk by half or more.
" CASE 1: Your risk of the complication is
estimated 5% (1 in 20). How much is your
threshold RR?


estimated 50% (1 in 2). How much is your
threshold RR?
estimated 0.1% (1 in 1000). How much is
your threshold RR?


" Summary of scenario: You suffered from
Disease A, and your doctor offer Drug X to
prevent complications.
" CASE 1: Your risk of the complication is estimated
at 5% How much is your threshold RR?
" CASE 2: 50%
" CASE 3: 0.1%


" Adverse effect of Drug X
" Any other drawbacks of the drug
" Cost, pain, inconvenience, taste of the drug and so
on.
" Your prognosis
" The physician’s experience of the drug in
clinical practise


value

evidence expertise


Nov. 16 2003
Seoul

" Cushing ulcer in the head injury
" In 1832, Cushing described gastric
ulceration associated with surgery and
trauma.
" Curling ulcer in the burn
" In 1842, Curling reported severe duodenal
ulceration and bleeding in the severe burn
patients.


" High incidence
" 15% in 1970s and 1980s in ICU patients (Ann
Intern Med 1987; 106: 562)
" Incidence of stress ulcer has decreased now.
" High mortality
" A case series study in 1960s reported nearly 90%
in mortality ! (Am J Surg 1969; 117: 523)


" Most of the stress ulcerations are superficial
mucosal erosions
" Such erosions are common in patients after
stressful event, such as major surgery and
trauma


" Gastric or Duodenal
ulcer. Mucosal defect is
obvious.
" Bleeding from a
submucosal vessel might
result in massive
bleeding.
" Deep ulcer might cause
perforation.


" Acute gastric mucosal
erosions. Superficial
mucosal defect.
" Oozing of blood from
capillary vessels.


Classical Stress Stress-related
Ulcer mucosal erosions

Both might cause important clinical complications


" Significant gastrointestinal (GI) bleeding
" Hemodynamic instability
" Anemia and Transfusion
" Gastrointestinal perforation
" Peritonitis
" => Laparotomy


" 2,252 ICU patient from 4 Canadian
centres.
" Definition of clinically significant bleeding
" Overt GI bleeding with hemodynamic change in
BP or HR, or progression of anemia
" Nearly half of the patients are associated in
cardiovascular operations. Several patient
subgroups were very few, such as trauma,
head injury, burn and transplantation.

outcome
factor A (+)
(+)
outcome Compare the
(-)
patients incidence of
outcome
factor A (+) outcomes
(-)
outcome
(-)

Follow-up

" Result: Two significant predictors were
found
" Mechanical ventilation at least 48 hrs
" Odds ratio: 15.6 (p<0.001)
" Coagulopathy (Plt <50,000, INR >1.5, PTT
>2.0)
" Odds ratio: 4.3 (p<0.001)


31 pts
with bleeding
847 pts
with any factor
815 pts
without bleeding 3.7%
2 pts
vs
with bleeding 0.1%
1405 pts
without any factor
1404 pts
without bleeding


" Though H2 receptor antagonists (H2RA), antacid
and sucralfate had been seemed to prevent
bleeding in earlier studies, a meta-analysis of RCTs
(JAMA 1996) showed that only H2RA were
effective in comparison with no prophylaxis (RR
0.44).
" H2RA might increase the risk of ventilator
associated pneumonia (VAP). Sucralfate might have
a protective effect for VAP comparing with H2RA
(RR 0.78, not statistically significant).

" Difficulty in conducting RCT of this topic.
" Low incidence of the outcomes: “Assuming a
bleeding rate of 2.0%... an RCT with 75% power
to detect 25% relative risk reduction (0.75 in RR)
in bleeding would have required approximately
19000 patients.” (Cook DJ in Intens Care Med
2001; 27: 347)
" Then they conducted a RCT of H2RA and
sucralfate in mechanically ventilated patients,
patients at the high risk of bleeding.

" 1,200 patients with ventilatory support of
longer than 48hrs in 16 Canadian centers.
" Ranitidine (50mg every 8hrs) vs Sucralfate (1g every
6hrs). Placebo-controlled.
" Central randomization with allocation concealment
" Patients, nurses, physicians, outcome accessors,
investigators and statisticians are all blinded until
the analyses completed


Treatment A

Incidence of
Group A
outcome

Patients

Incidence of
Group B
outcome
Randomization
Treatment B


Ranitidine + placebo

bleeding 10/596
596 pts
pneumonia 114/596

1200 pts
bleeding 23/604
604 pts
pneumonia 98/604
Randomization
placebo + Sucralfate


Bleeding Pneumonia

Ranitidine 1.7% (10/596) 19.1% (114/596)

Sucralfate 3.8% (21/604) 16.2% (98/604)

RR 0.44 (p<0.02) 1.18 (p=0.19)
In the patients at high risk for stress ulcer (>48hr mechanical
ventilation), ranitidine decreased clinically signiﬁcant GI bleeding
comparing with sucralfate (RR 0.44). It did not increase the risk of
ventilator associated pneumonia signiﬁcantly.
Mortality in ICU and ICU stay were same: 23.5% vs 22.8%, 9 days in
both group.

" 1077 ICU patients ventilated at least 48hrs
" The incidence of clinically important GI
bleeding was 2.8% (30/1077).
" Independent significant predictor of
clinically important GI bleeding
" Max S-Crn level: OR 1.16
" Enteral nutrition: OR 0.30
" Administration of ranitidine: 0.39

!  The controversy continues...

Nov. 16 2003
Seoul

" Ranitidine increased the risk of VAP
comparing with scuralfate (RR 1.35: 1845 pts
from 8 studies)
" Both ranitidine and sucralfate did not prevent
GI bleeding in comparison with placebo (5
studies, 398pts from 5 studies and 54 pts from
1 study, respectively)


" Will you give stress ulcer prophylaxis to the
patients...
" A post-CABG patient without coagulopathy
" An intubated elderly patient of nosocomial
pneumonia


" the framework of Evidence-based
Medicine
" Evidence+Expertise+Values
" the history and spectrum of the stress
ulcer
" Ulcer=> Acute superficial erosion
" GI bleeding is the most common
complication.


" the incidence and risk factors of the ulcer
" The incidence of clinically significant GI bleeding
is around 2% in general ICU patients. The risk of
significant GI bleeding in ventilated patients is
around 4%.
" the treatment effect of the prophylaxis
" H2RA reduces the incidence of GI bleeding less
than half. The efficacy of ranitidine is questioned
in recent meta-analysis.


Stress Ulcer Prophylaxis in ICU

More Related Content

What's hot

Viewers also liked

Similar to Stress Ulcer Prophylaxis in ICU

More from 敏雄 福岡

Recently uploaded

Stress Ulcer Prophylaxis in ICU

More from 敏雄福岡