ICU patients have marked risk for stress GIT ulceration, in this lecture, I discuss the recent measures of prophylaxis

1. By
Mohamed Abuelnaga,MD
Suez Canal University

2. Background And Introduction
Pathophysiology
Clinical Presentation
Risk Factors For SRMD
Drugs Used For SUP
Adverse Effects Of SUP
The Role Of Enteral Feeding In SUP
Current Guidelines

3. Stress-related mucosal damage (SRMD) :is a term used
to describe an acute, erosive, inflammatory insult to
the upper gastrointestinal tract associated with critical
illness.
It was described for the first time in 1969 when small
focal lesions were found in mucosa of gastric fundus
during postmortem examinations in 7 (out of 150)
critically ill patients
In old studies:74–100 % of critically ill patients have
SRMD within 24 hours of admission
Now: the condition becomes infrequent (0.6 and 4 %)
of ICU patients.

4. SRMD occur mostly in critically ill patients as a result
of impaired gastric mucosal blood flow:
A)systemic hypotension and/or vasopressor therapy
B) local alterations, e.g., reduced splanchnic blood
flow because of PEEP in MV patients.
Leading to :
@ tissue damage due to ischemia.
@ reduced production of various protective
substances such as mucus, phospholipid, and
bicarbonate that help in gastric mucosal protection

5. @ reduced nitric oxide levels which act as a
vasodilator, with increase in the levels of endothelin-
1, which acts as a strong vasoconstrictor which can
cause a mucosal damage.
But ,all these mechanisms are insufficient to cause
mucosal ulceration and bleeding.
Several authors stated that :the addition of gastric acid
is mandatory with the presence of gastric ischemia to
cause SRMD
SO it is logical to use antacids as a stress
ulcer prophylaxis

8. SRMD can present clinically as :
1-asymptomatic superficial lesions found incidentally
during endoscopy: (most of patients)
2-occult gastrointestinal bleeding causing anemia.
3-Overt gastrointestinal bleeding: hematemesis,
bloody GIT aspirate or melena:25 % of critically ill
patients
4-clinically significant gastrointestinal bleeding: overt
GIT bleeding and either hemodynamic compromise,
or the requirement for blood transfusion, or surgery

9. Gastric antral erosion Pyloric ulcer with adherent clot

10. Cook et al.
(1994)
-mechanical
ventilation
-Coagulopathy
NB: Absence of
these RF,⇓⇓the
risk < 0.1%
Krag et al. (2015)
-liver failure
-renal failure ,HD
-coagulopathy
-≥ 3 comorbidities
NB: mechanical
ventilation is not a risk
factor
Risk factors with low
degree of evidence
-Head Trauma
-Extended Operations
>4 H
-Sepsis
-Hypotension
-Advance Age
-NSAIDs,seroids
-Male Sex

11. PPIsH2RBssacralfate
inhibition of H+/K+ ATPase
enzyme at the secretory
surface of the parietal cell⇨
inhibition of H+ ions and
thereby⇧ pH of the gastric
contents.
blocking of histamine binding
to its G-protein coupled
receptor on the gastric
parietal cells⇨⇓acid
production and gastric
secretions.
Forms physical
cytoprotective barrier at
the ulcer site which
protect gastric mucosa
from acid and pepsin
-rebound acid hypersecretion
after discontinuation
-diarrhea
-interstitial nephritis
-pneumonia
-high dose IV omeprazole
(hearing and vision
disturbances, seizures)
-hypophosphatemia
-osteoporosis and fractures
-thrombocytopenia
(especially in pediatrics)
-confusion (especially in
elderly),
-interstitial nephritis,
-rapid infusion-related
hypotension and sinus
bradycardia,
- pneumonia
-constipation
-occlusion of the feeding
tube
-⇓K, PO4
-aluminum toxicity
(especially in the
presence of renal
dysfunction
-drug binding warfarin,
phenytoin, digoxin,
fluoroquinolones,
theophylline, quinidine,
L-thyroxin

14. Stress ulcer prophylaxis act by reduction of
gastric acidity environment, which has a role in
host defense mechanism, with an intragastric
PH< 4 being suitable for bactericidal activity.
Reduced acidity will cause infection
development:
1)Infection related ventilator associated
complications (IVAC).
2)Clostridium difficile associated colitis and
diarrhea.

15. 1- antacids increase intra-gastric PH, thus
increase the chances of gastric colonization with
pathogenic organisms .
2-contamination of the oropharyngeal area by
reflux of gastric fluid, with subsequent aspiration
of the oropharyngeal bacteria to the lower airways.
Laheij et al.(2004): the use of PPIs is associated
with significant increase in the risk of community
acquired pneumonia development.
Cook et al. (2009) :reported a trend towards
increased rates of pneumonia with the routine use
of H2RBs .

16. Treatment with PPI and H2RA is associated with
increased risk for post-stroke pneumonia, but treatment
with muco-protective agents is not

17. Yearsley et al. (2006):
evaluated a case-control study of 303 patients
admitted to a general medical ward; found a
significant increase in the risk of acquiring C.
difficile infection in patients using PPIs
Zilberberg et al.(2009) :evaluated the data of
65000 MV ICU patients. They found that C.
difficile infection developed in > 5% of the
patients due to decreased gastric acidity

18. Ephgrave et al. (1990): mentioned that liquid
nutrient help in prevention of stress ulcers,
liquid nutrient work as a buffer for the gastric
acid increasing the mucosal blood flow, and
enhancement of prostaglandin and mucus
secretions
Bonten et al. (1994) : continuous enteral
nutrition is more effective in increasing
intragastric PH than PPIs and H2RBs In rats

19. In patients receiving EN in the ICU, pharmacologic SUP
showed no beneficial effect on GI bleeding, overall
mortality, Clostridium difficile infection, length of stay
in the ICU or duration of mechanical ventilation, but was
associated with an increased incidence of HAP

20. SO what to do?

22. Old guidelines:
ASHP (1999): Sucralfate or H2RAs
SSC (2008): use either H2RA (1A) or PPIs (1B)
EAST (2008): use either H2RAs or PPIs(Level 1)
SSC(2012): use PPIs rather than H2RAs (2C)
DASAIM (2014): do not use SUP routinely for adult
critically ill patients outside the context of trials (1C)
SSC(2016):PPIs or H2RAs (low quality of evidence)

23. Prepared jointly by the Surgical Critical
Care and Medical Critical Care Services
at Orlando Regional Medical Center.
Revised 1/15/2004, 12/7/2005,
10/11/2009, 9/15/2011, 11/2/2017

24. Potential Risk FactorsAcute Risk Factors
1- Concomitant use (NSAID)
2-Concomitant or recent
corticosteroid use
3-History of upper GI haemorrhage,
peptic ulcer disease, or gastritis
1-MV (>48 hours) without enteral
nutrition
2-Coagulopathy(plat<50,000
mm3, INR >1.5, or aPTT > 2
times control)
3- Hypo perfusion (shock, or
organ dysfunction)
4-High-dose corticosteroids
(>250 mg/day hydrocortisone or
equivalent)
5- Significant burn injury (total
body surface area 20%)

25. Level 2
➢ Chemoprophylaxis for stress ulcer prevention is indicated in
patients with acute risk factors.
➢ Discontinue therapy when patients no longer have acute risk
factors.
➢ Consider discontinuing therapy when a patient is tolerating full
enteral feeding.
➢ Sucralfate is an acceptable alternative to a H2RA and may decrease
the incidence andseverity of ventilator associated pneumonia.
➢ A PPI is an alternative to a H2RA or Sucralfate in situations where
these agents cannot be used.

26. Level 3
➢ A H2RA can be considered in patients that are NPO and
have at least two potential risk factors for stress
ulceration.
Doses:
1-H2RA:
Ranitidine :50mg/8h slowly i.v. or 150 mg qd
oral
2) PPI:
omeprazole: 40 mg qd i.v. or or oral
3) Mucosal protective agents:
Sucralfate: 1-2 gm/6h oral

27. Results:
1-PPIs are probably more effective for preventing clinically
important gastrointestinal bleeding than H2RAs.There were no
convincing differences among H2RA, sucralfate, and placebo.
2-PPIs probably increase the risk of developing pneumonia
compared with H2RAs,sucralfate and placebo (all moderate quality).
3-Mortality is probably similar across interventions (moderate
quality).
57 trials enrolling 7293 patients

28. In this updated systematic review, we were able to refute a relative change of
20% of mortality when prophylactic PPI or H2RA were compared with placebo
or no prophylaxis in adult ICU patients. GI bleeding was reduced with PPI or
H2RA, but firm evidence for a reduction in clinically important GI bleeding was
not found. The effects on serious adverse effects, myocardial ischemia,
pneumonia, and CI. Difficile enteritis remain inconclusive.
42 trials randomising 6899 ICU patients

30. Methods:
2292 unique records identified, 129 records included
reporting on 121 studies
Results and Conclusion:
1-antacids, sucralfate, and H2 receptor antagonists might
be more effective in preventing upper GI bleeding in ICU
patients compared with placebo or no prophylaxis.
2- Evidence of low certainty suggests that proton pump
inhibitors might be more effective than H2 receptor
antagonists
3- Evidence of low certainty suggests that Nosocomial
pneumonia occurred in similar proportions of participants
taking H2 receptor antagonists or proton pump inhibitors;
larger high-quality RCTs are required to be assessed

32.  Critically Ill Patients Are At Increased Risk For SRMD
 SUP Has Fatal Risks
 Do Not Start SUP Unless When Indicated
 Try Hard To Manage The Patients To Overcome The Risk
Factors:
 Optimal Fluid Resuscitation
 Improving Splanchnic Hypo-perfusion
 Early Provision Of Enteral Feeding
 Weaning From MV As Early As Possible
 Discontinue SUP When No Longer Indicated

34. THANK YOU