Stress ulcers are mucosal erosions which primarily occur in the
stomach, but can also be found in the distal esophagus or duodenum.
They can develop within hours of a trauma or the onset of a critical
illness. Critically ill patients who bleed from these lesions have a
five-fold increase in mortality compared with patients who do not
bleed. Discussion about prophylaxis of stress ulceration in intensive
care unit patients has been posted here is the detail:
INTRODUCTION
* Stress ulcerations are mucosal erosions that generally occur in the
fundus and body of the stomach, but sometimes develop in the antrum, duodenum,
or distal esophagus.
* They tend to be shallow and cause oozing of blood from superficial
capillary beds, but deeper lesions can erode into the submucosa, causing
massive hemorrhage and/or perforation.
The risk of stress ulceration depends upon the severity and type of a patient's
underlying illness.
* Studies of various intensive care unit populations have estimated the
risk of stress ulceration complicated by clinically significant bleeding at 1.5
to 15 percent.
* Stress ulcerations are the most common cause of gastrointestinal (GI)
bleeding in intensive care unit (ICU) patients, and the presence of GI bleeding
due to these lesions is associated with a five-fold increase in mortality
compared to ICU patients without bleeding.
Considerable effort and expense are devoted to the prevention of stress
ulcerations in pati
ents in the ICU because the consequences of GI bleeding can be severe.
* However, continued use of stress ulcer prophylaxis in hospitalized
patients who have been discharged from the ICU is generally unwarranted and
alarmingly common.
PATHOPHYSIOLOGY
* Erosions begin to develop in the proximal regions of the stomach within
hours of major trauma or serious illness.
* In one study, endoscopy performed within 72 hours of a major burn or
cranial trauma revealed evidence of acute mucosal disease in 75 to 100 percent
of patients.
* Up to 50 percent of these early mucosal lesions have endoscopic evidence
of recent or ongoing bleeding,
o but only a small percentage of these patients experience
hemodynamic compromise due to acute blood loss.
Stress ulcerations that evolve after the first several days of hospitalization
tend to be deeper and occur more distally within the GI tract.
* As an example, one study of 67 patients with GI bleeding which occurred a
mean of 14 days after admission found that duodenal ulceration was the most
common source of bleeding.
* It is uncertain if early and late ulcerations have the same
pathophysiology, but both types are thought to result from derangements in the
balance between gastric acid production and mucosal protective mechanisms.
One or more of the following processes may be involved:
Hypersecretion of acid
* Hypersecretion of acid due to excessive gastrin stimulation of parietal
cells is seen primarily in patients with head trauma.
* Acid secretion tends to be normal or subnormal in most other patients, in
whom stress ulceration results from a breakdown of mechanisms normally
protecting the gastric mucosa from the effects of acid.
Defects in gastric glycoprotein mucus
* The stomach normally is protected by a glycoprotein mucous layer, which
both forms a physical barrier to hydrogen ion diffusion and traps bicarbonate,
allowing neutralization of gastric acid in the area adjacent to the stomach
wall.
* In critically ill patients, increased concentrations of refluxed bile
salts or the presence of uremic toxins can denude the glycoprotein mucous
barrier and permit gastric injury.
Ischemia
* Shock, sepsis, and trauma can lead to impaired perfusion of the gut.
* Experimental models of shock suggest a relationship between gastric
mucosal ischemia and diminished secretion of protective mucus and bicarbonate.
H pylori
* The influence of infection with H. pylori on the development of stress
ulcers in the intensive care unit has not been well studied.
* One multicenter case-control study identified 29 patients with acute
upper GI bleeding following admission to an intensive care unit, and found that
these patients were more likely than nonbleeding ICU patients to have evidence
of H. pylori infection (36 versus 16 percent).
* In a separate report, a statistically nonsignificant trend toward an
increased risk of macroscopic gastrointestinal bleeding was observed among 67
H. pylori positive patients compared to 33 H. pylori negative controls.
* Furthermore, nurses in the intensive care unit were more likely to be
infected with H. pylori than age-matched controls (40 versus 19 percent),
suggesting the possibility of nosocomial transmission.
RISK FACTORS
A prospective multicenter cohort study of 2252 ICU patients identified two
major risk factors for clinically significant bleeding due to stress ulcers:
1. mechanical ventilation for more than 48 hours (odds ratio 15.6); and
2. coagulopathy (odds ratio 4.3).
* The risk of clinically important bleeding in patients without either of
these risk factors was only 0.1 percent.
A number of smaller studies have reported additional risk factors for stress
ulcerations, including :
* Shock
* Sepsis
* Hepatic failure
* Renal failure
* Multiple trauma
* Burns over 35 percent of total body surface area
* Organ transplant recipients
* Head or spinal trauma
* Prior history of peptic ulcer disease or upper GI bleeding
PROPHYLACTIC AGENTS A variety of medications may be used to reduce the
incidence of stress ulceration, including antacids, H2 blockers, sucralfate,
proton pump inhibitors, and prostaglandin analogs.
Antacids
* The action of antacids are to decrease gastric acidity by direct
neutralization of stomach acid.
* Antacids are generally considered effective in the prevention of stress
ulceration because numerous studies have shown roughly equivalent outcomes with
these agents and H2 blockers.
* However, one meta-analysis found only a nonsignificant trend toward
efficacy with antacids compared to placebo.
Drug costs are low, but these agents require administration of 30 to 60 mL
orally or via nasogastric tube every one to two hours.
* The increase in nursing costs necessary for such administration negates
some of the potential cost savings.
* Side effects of antacids can include hypermagnesemia, hypophosphatemia,
constipation, diarrhea, nasogastric tube obstruction, and an increased risk of
nosocomial pneumonia.
H2 blockers
* H2 blockers raise gastric pH by decreasing the stimulatory effects of
histamine on parietal cell acid secretion.
* Their effectiveness in preventing stress ulceration has been documented
in most (but not all) trials.
* One meta-analysis, for example, reported a significantly lower risk of
clinically significant GI hemorrhage with cimetidine versus placebo (3 versus
15 percent).
Administration of H2 blockers by continuous infusion provides better control of
gastric pH than bolus infusion, but is not more effective in preventing
clinically significant bleeding.
* H2 blockers are also effective if given orally or via nasogastric tube.
* H2 blockers are generally well tolerated, but occasionally the drugs may
produce interstitial nephritis, confusion, or thrombocytopenia.
* Furthermore, the pharmacokinetics of drugs such as theophyline and
warfarin may be significantly affected by cimetidine but not other H2 blockers.
* The costs of H2 blockers can be substantial, and dosing via continuous
infusion may increase the number of intravenous catheters required by the
patient.
Sucralfate
* Sucralfate is a complex polyaluminum hydroxide salt of sucrose sulfate
which exerts its effects via coating and protection of the gastric mucosa
rather than through neutralization or inhibition of gastric acid.
* Sucralfate becomes highly polar at acid pH and binds preferentially to
the granulation tissue of exposed ulcer beds, protecting them from further
damage from acid, bile salts, or pepsin.
* The most rigorous randomized trial to date studied 1200 mechanically
ventilated patients and found a significantly higher risk of clinically
important GI bleeding with sucralfate versus H2 blocker (ranitidine) (3.8
versus 1.7 percent).
* This trial was important because of its large sample size, the fact that
care givers, research personnel, and analysts were blinded to treatment
assignments, its high rates of compliance, and the fact that clinical bleeding
and pneumonia were strictly defined.
* One meta-analysis described similar findings, but reported a reduced
mortality rate with sucralfate versus antacids and H2 blockers, possibly due to
the less frequent development of nosocomial pneumonia (see below).
* Other, less rigorous trials have been done and in general reported that
sucralfate and H2 blockers have similar efficacy.
Sucralpate is generally well tolerated.
* Elevations of plasma aluminum concentration have not been observed in
intubated patients receiving 6 grams/day of sucralfate for 14 days, even in the
presence of renal impairment.
* Costs may differ substantially between institutions, but the use of
sucralfate generally is less expensive than the use of parenteral H2 blockers.
Proton pump inhibitors
* Proton pump inhibitors, such as, omeprazole and others, contain a
reactive sulfhydryl group that forms a disulfide bond with a cysteine residue
on the H-K-ATPase pump, thereby inactivating the enzyme.
* Data regarding the efficacy and potential adverse effects of these drugs
in the prevention of stress ulceration are less extensive than the sucrafate,
H2 blockers, and antacids.
* Short-term use of proton pump inhibitors is rarely associated with
significant side effects.
* Hypotheses regarding an increased incidence of nosocomial pneumonia due
to elevations in gastric pH have not been adequately tested.
The ability of omeprazole oral suspension to decrease stress-induced GI
bleeding was assessed in two prospective, open-label trials of mechanically
ventilated with at least one additional risk factor for stress-related mucosal
damage.
* In the first study, 75 patients received two doses of omeprazole oral
suspension 40 mg six to eight hours apart, followed by 20 mg/day delivered via
nasogastric tube.
o There were no episodes of bleeding and no evidence of toxicity.
o Similar results were noted in a subsequent study of 60 patients
treated with omeprazole administered using the dosing regimen described above.
The relative efficacy of intravenous omeprazole, intravenous H2 blocker, and
sucralfate in preventing bleeding associated with stress ulcers was evaluated
in a prospective, randomized, three-arm trial published in abstract form.
* Omeprazole (40 mg every 12 hours) and ranitidine (150 mg/day) were
administered intravenously; sucralfate 1 g every six hours was administered by
nasogastric tube.
* The frequency of upper gastrointestinal bleeding was similar in patients
treated with ranitidine and sucralfate (10.5 percent and 9.3 percent,
respectively).
One study randomized 67 high-risk patients to prophylaxis with either
intravenous H2 blocker or oral omeprazole.
* A significantly larger proportion of patients in the ranitidine group
developed clinically important bleeding (31 versus 6 percent); however the
ranitidine group had more risk factors for GI bleeding despite randomization,
potentially confounding the results of the study.
* A subsequent larger trial compared oral omeprazole and intravenous the
cimetidine in 359 ICU patients, and noted similar rates of GI bleeding in both
groups (4.5 versus 6.8 percent, respectively;) .
* It has been suggested that oral PPI therapy may be more cost-effective
than intravenous cimetidine for the prevention of stress ulcer-related
gastrointestinal bleeding.
Prostaglandin analogs
* Prostaglandin analogs such as the mesoprostol have both antisecretory and
cytoprotective effects.
* The latter may result from capillary bed vasodilation, which protects
against local ischemia.
* Several small trials and animal experiments suggest that misoprostol may
be as effective as H2 blockers or antacids, in preventing stress ulceration,
but the paucity of data and the propensity to cause diarrhea limit its clinical
use in this setting.
Nutrition
* Several studies have reported that enteral nutrition may reduce the risk
of bleeding due to stress ulcerations.
* As an example, one study of 526 seriously burned patients compared
treatment with antacids and cimetidine, versus enteral nutrition in the absence
of prophylactic medications.
* The rate of overt GI hemorrhage was significantly lower in the group that
received enteral nutrition as the sole form of GI prophylaxis (3.3 versus 8.3
percent).
A separate study analyzed data from 1077 critically ill Canadian patients who
required mechanical ventilation for more than 48 hours.
* Patients who received enteral nutrition were significantly less likely to
develop an upper gastrointestinal hemorrhage (risk ratio 0.30; 95% CI
0.13-0.67).
* However, treatment was not randomized, so it is possible that patients
with a lower intrinsic risk of bleeding were better able to tolerate enteral
feeding.
The effect of enteral nutrition is not mediated by an increase in gastric pH.
* Nutrition may prevent exhaustion of gastric epithelial energy stores and
thereby prevent necrosis and ulcer formation; this mechanism may explain the
protective effect against stress ulceration that has been reported with total
parenteral nutrition (TPN).
NOSOCOMIAL PNEUMONIA
* The major concern about prophylactic therapy for stress ulceration has
been the potential increased risk of nosocomial pneumonia.
* Agents that raise gastric pH may promote the growth of bacteria in the
stomach, particularly gram-negative bacilli that originate in the duodenum.
* Esophageal reflux and aspiration of gastric contents along the
endotracheal tube may lead to endobronchial colonization and to pneumonia.
A number of studies have documented an increased frequency of nosocomial
pneumonia in patients treated with H2 blockers or antacids as compared with the
sucralfate.
* As an example, one study randomized 258 intubated patients to treatment
with one of the following regimens: ranitidine at a rate of 6.25 mg/hour,;
antacid 20 mL of antacid via nasogastric tube every two hours; or 1 gram of
sucralfate via nasogastric tube every four hours.
* Nosocomial pneumonia occurring four or more days after intubation was
significantly less frequent in patients receiving sucralfate (five versus 16
percent with antacids and 21 percent with ranitidine).
* No significant differences in macroscopic gastric bleeding were noted
among the three treatment groups.
* A subsequent study of 1200 mechanically ventilated patients randomized to
prophylaxis with either 1 gram every 6 hours of sucralfate or 50 mg every 8
hours of intravenous H2 blocker found only a nonsignificant trend toward a
lower incidence of ventilator-associated pneumonia among sucralfate-treated
patients.
SUMMARY
* Stress ulcers are mucosal erosions which primarily occur in the stomach,
but can also be found in the distal esophagus or duodenum. They can develop
within hours of a trauma or the onset of a critical illness. Critically ill
patients who bleed from these lesions have a five-fold increase in mortality
compared with patients who do not bleed.
* Stress ulcers are believed to be caused by an imbalance between gastric
acid production and mucosal protection mechanisms. Mucosal ischemia may be an
important cause in patients with underlying shock, sepsis, and trauma.
* Definite risk factors for the development of stress ulcers include
mechanical ventilation for more than 48 hours and coagulopathy.
o In addition, possible risk factors include shock, sepsis, hepatic
and renal failure, multiple trauma, burns (>35 percent total body surface
area), organ transplantation, head and/or spinal trauma, and a prior history of
upper GI bleeding or peptic ulcer disease.
* Pharmacologic agents available for stress ulcer prophylaxis include
H2-antagonists, antacids, sucralfate, prostaglandin analogs, and proton pump
inhibitors (PPIs).
o It is widely suggested that oral PPIs are for patients who are able
to receive enteral medications, rather than intravenous H2 blockers, because
they are superior at maintaining gastric pH >4, are not limited by tolerance,
and may be more cost-effective.
o In contrast, intravenous H2 blockers in for patients who cannot
receive enteral medications, rather than intravenous PPIs.
o This is based on the opinion that the far greater cost of
intravenous PPIs outweighs the nominally greater efficacy that may exist.
* Stress ulcer prophylaxis should be discontinued after discharge from the
ICU.
* The role of enteral nutrition in stress ulcer prophylaxis is uncertain.
o Early enteral nutrition contributes to stress ulcer prophylaxis;
o however, it alone cannot be recommended as sole stress ulcer
prophylaxis in high risk patients.
* Whether acid suppression therapy confers an increased risk of nosocomial
pneumonia is uncertain due to conflicting published data.
Posted by jitendraagrawal2000 at 6:01 AM
http://www.surgerysearch.blogspot.com/
Dr. Jitendra Agrawal, Kanpur, India.
