New Approaches In The Management Of Stress Induce Ulcer - Does Prophylactic Measure Can Cure SIU ???

STRESS INDUCED ULCERATION:

Stress ulceration which is also known as stress related mucosal damage (SRMD), is self-explanatory term which describe its range of pathology contributing from the acute erosion to severe bleeding. Stress ulcer are most commonly found in gastric part that can be precipitate by any form of stress due to the disruption in mucosal barrier. 

It remain asymptomatic when begin in the form of erosive gastritis with superficial lesion and gradually become symptomatic wit sever GI bleeding.

Stress can induce ulcer ???

Types of stress induced ulcer:

Two types of SRMD are describe below:

i.                    Curling ulcer:  systemic burns leading to ulcer which is known as curling ulcer.

ii.                   Cushing ulcer: injury or specifically traumatic brain injury induce ulcer, named as cushing ulcer.

Etiology(risk factors):

Following are the risk factors of stress factors of stress induced ulcer:

i.                    Long term mechanical ventilation i.e. more than 48 hours.

ii.                   Septic shock or sepsis.

iii.                 Patient using vasopressor and corticosteroid ( greater than 250mg/day)

iv.                 Hepatic renal and multiorgan failure.

v.                   Average or below average sanitation during the ICU stay.

vi.                 Gastrointestinal bleeding within last 12-24 months.

vii.               Burns that covers 30% of body surface area.

viii.        Any alteration in coagulation profile that is platelets counts less than 50,000, value of international normalize ratio is not less than 1.5 and PTT greater than two time the control value.

Pathophysiology:

Any deterioration in mucosal barrier next to systemic stress can result in erosion of gastric mucosa (superficially only). Enhancement of concentration of refluxed uremic toxins and bile salts which can impaired the protective mucosal barrier are the outcome of acute critical illness and that can ultimately destroy the mucosal glycoprotein. This destruction are resulted from increased gastrin secretion secondary to the increase level of gastric acid.

Protection of barrier may lead to decrease in perfusion of gastric submucosa in hospitalized patients.

Patients which neurological trauma are more prone to stress ulcer. Also, acute respiratory distress syndrome are also the major cause SRMD.

PROPHYLAXIS OF STRESS INDUCE ULCER:

It’s not easy enough to identify the
efficacies of prophylactic regimens use for stress induce ulcers because of
variation in desire PH goals and interpretation of GI bleeding. Due to the high
mortality and morbidity rate correlate with bleeding episodes from stress ulcer
resulting in developing of various strategies to prevent this condition.
Different regimens are use traditionally, all of these regimens are differ in
their pharmacological mechanism of action, efficacy of drug, adverse drug events,
administration and cost.

 
Cimetidine and antacids doesn’t decreases the occurrence
of mucosal lesions in critically ill patients when use prophylactically, but it
is quiet effective in preventing the progression of mucosal lesion to more
dangerous form which untimely prevent significant bleeding. intravenous acid
suppression therapy, histamine receptor antagonist, proton pump inhibitor and
sucralfate administration through nasogastric tube (4-6gram/day in divided
doses) has been proven clinically important for prevention of ulceration
induced by stress in critically ill patient. All are describe one by one in the
following lines.  

ANTACIDS :

The traditional prophylactic regimen for stress ulcer consists of acid suppressing drugs which is administered via nasogastric route for maintaining intragastric PH not less than 3.5. The desire PH can only be achieve by administration of 20ml-40ml bolus infusion. Additional bolus can also be required for attaining the required PH.

Increased chances of aspiration and hemorrhage are the drawback of this therapy particularly in the presence of nasogastric tube, which restricted its use. Precipitation of hyphosphatemia, hypermagnesemia or metabolic alkalosis by virtue of increased level of magnesium and aluminum are also remain point of concern.

HISTAMINE RECEPTOR ANTAGONIST (H2 RECEPTOR ANTAGONIST):

This class of drug have greater importance in prophylaxis of stress ulcer through antagonizing the histamine receptor and decreasing the acid secretion in critically ill patients. It is administered by bolus injection because from various studies it was proved that, comparatively continuous infusion control acidity more efficiently then Intermittent bolus injection and bring PH to desire range in patient.

Commonly use H₂ receptor antagonist are cimetidine , famotidine and ranitidine, their choice can be depend upon relative potency, onset , duration of action and side effects.

These drugs are equally efficious but differ in side effects for example cimetidine have more side effects, it causes gynocomastia, hepatorenal toxicity and CNS side effects. After bolus infusion hypotension by cimetidine also reported. It also alter the metabolism and renal clearance of various drugs used in hospitalized patients secondary to the alteration in microsomal drug metabolism system. So famotidine become the drug of choice in stress induce ulcer because it doesn’t have any hemodynamic effects nor disturb the hepatic metabolism. In addition, ranitidine doesn’t found any adverse effects on platelet production. Along with safety profile of these drugs, it’s BID dosing and inhibitory effects on the secretion of gastric acid make these drugs more popular for the prevention of stress induced ulcer.

 

M1 CHOLINOCEPTOR ANTAGONIST:

Through different studies it is shown that pirenzipine affects the gastric acid release in hospital admitted patients. Its comparsion with rantidine describe that both have same effects at the PH of gastric aspirates, through increasing the PH, but somehow rantidine become clinically important.

One major problem with this drug is less specificity of receptor in critically ill patient so due to blockade of M₂ cholinoceptors after rapid infusion result in tachycardia that will worsen the patient condition. Furthermore it efficacy in decreasing the GI bleeding has not be found to the greater extent so its use is limited in stress induce ulcer.

PROTON PUMP INHIBITOR: 

Proton pump inhibitor produces their effect by inhibiting the proton pump which decrease the acid levels. Most potent and clinically important proton pump inhibitor use chronically in peptic diseases for balancing the acid release, is omeprazole, that’s also are under clinical trials as prophylactic agents in stress  induce ulcer. It have greater acid suppression activity than H₂ receptor after 24 hours of intake.

Omeprazole should be taken in 40mg dose per day by either nasogastric route or orally for attaining PH greater than 4.0.

Along with potency, long duration of action and better patient compliance make it better choice for the prophylaxis of stress induced ulcer.

Like pirenzipine, its efficacy in critically ill patients remain controversial.

CYTOPROTECTIVE AGENTS: 

Sucralfate , alumunium salt of sucrose and octasulfate , administered orally, having several  mechanism of action but none of machnism define its effects on PH.

i.                    Initially its mechanism was proposed to be direct occlusion in the passage of hydrogen ion through the membrane but on the basis of current evidence its possible mechanism may be the increment of release in PGF₂ in gastric mucosa, that give cytoprotctive action and increased mucosal blood flow .

ii.                   Its effect in repairing of injury may also noticeable by enhancing the mucous proliferative zone at ulceration site through increasing the mucus output and its binding to anigiogenic factors and growth factors.

Because of its little absorption from Gastrointestinal tract it shows minimal localand systemic side effects.

Dose:

1gram of sucralfate administered via feeding tube or orally four times a day in suspension form.

 

NEW APPROACHES IN THE PROPHYLAXIS

OF STRESS INDUCED ULCER:

• I.  USE OF CHLOREALLA VULGARIS ( UNICELLUAR GREEN ALGAE) IN PREVENTING STRESS INDUCED ULCER:

Chlorealla vulgaris tested pre clinically by administrating it in powder form in water immersion restraint stress induced and in cysteamine induced ulcer models. It have effects on endogenous interleukin-I and have profound effects on gastric mucosa and diminishing the ulcernogenic stimuli. It is also proposed that anti stress induced ulcer of this unicellular green algae are due to its effects by augmenting T lymphocytes or/and macrophages participant host defense.  So it may prevent the stress induce ulcer through immune-brain gut axis and preventing through its unique charactertics.

 

II.  MELATONIN USE AS PROPHYLACTIC AGENT IN STRESS INDUCE ULCER :

Melatonin in a dose depended manner decreasing the chances of stress induced ulcer at a dose of 60mg per kg body weight. In comparison with already used and marketed antiulcer agents such as ranitidine and omeprazole it is found to be more effective than ranitidine but less efficious than omeprazole as a prophylactic agent in stress induce ulcer. While it comparison with other antioxidants are also become important because it was more potent than glutathione and equally potent with alpha tocopherol in preventing the stress ulcer.

Stress ulcer caused by oxidative damage resulted from hydroxyl radicle (OH). Melatonin shown its effects on scavenging the hydroxyl ion in stress condition.

 

MANAGEMENT OF STRESS INDUCED 

ULCER:

Lack of prophylactic measures and critical clinical condition can result in gastrointestinal bleeding. The first step in the management of stress induced ulcer is transfusion of blood, volume resuscitation and correction of the coagulation profile and coagulopathy. After appropriate and proper resuscitation gastric lavage should be break down at room temperature and also decreases the gastric distention along with removing the clots, that will decreases the chances of aspiration. Removing clots play role in maintaining the homeostasis by reducing local fibrinolytic activity through gastric lavage.

If bleeding not control then adopted one of following two approaches for controlling the submucosal blood flow and maintaining the hemostasis.

i.                    Administer intravenous vasopressin in the dose of 0.5-1.0units/min but it can result in cardiac side effects that are cardiac arrhythmia and ischemia.

ii.                   Or if available administer intravenous somatostatin infusion in the dose of 250micrograms / hour.