ICU Book - 4th Ed. -  Marino
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ICU Book - 4th Ed. - Marino

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skin wounds with a chemical agent that was used to treat sewage, and observed a marked decline in suppurative wound
infections. Lister’s observations were published in 1867 in a treatise entitled On the Antiseptic Principle in the Practice of Surgery (9). In
the following excerpt from this treatise, Lister describes the chemical agent that he used:

The material which I have employed is carbolic acid, a volatile compound which appears to exercise a peculiarly destructive influence
upon low forms of life, and hence is the most powerful antiseptic with which we are at present acquainted.

As indicated, the very first antiseptic agent used in clinical medicine was an acid. Thus, Joseph Lister not only discovered the benefits of
antisepsis in preventing infections, he also discovered the benefits of acids in eradicating infectious microbes. (In recognition of Lister’s
discoveries, his name is now immortalized by a mouthwash, Listerine!)

Antiseptic Effects of Gastric Acid
The influence of gastric pH on the growth of a pathogenic organism is shown in Figure 5.3 (10). The pathogen in this case is
Salmonella typhimurium, a common cause of infectious enteritis in humans. The graph in Figure 5.3 shows the survival of S.
typhimurium in gastric juice at three different pH levels. The organism thrives at a pH of 4. However, survival begins to decline at a pH
of 3, and the organism is almost completely eradicated at a pH of 2. These survival curves indicate that gastric secretions are
bactericidal when the pH falls below 4. The normal pH of gastric secretions is well within this range.


FIGURE 5.3 The influence of gastric pH on the survival of Salmonella typhimurium, a common cause of infectious enteritis. (From Reference 10)

Considering the bactericidal effects of gastric acidity, it is likely that gastric acid serves as an antimicrobial guardian that protects the GI
tract from unwanted pathogens. The benefits of gastric acid as an infection control device are summarized below.
1. Gastric acid eradicates pathogens that are ingested in contaminated food products. This is demonstrated in studies showing that

reduced gastric acidity is associated with an increased incidence of infectious gastroenteritis from Salmonella and Campylobacter
species (8,10–13). Food processing techniques do not always remove infectious organisms, and gastric acid serves as a built-in
backup mechanism for disinfecting the food we eat.

2. Gastric acid can block the transmission of illnesses via the fecal-oral route. This is demonstrated by the association of gastric-acid
suppressing drugs with Clostridium difficile enterocolitis (14). This is an important and often-overlooked complication of drugs that
suppress gastric acidity, and will be described in more detail later in the chapter.

3. Gastric acid eradicates microorganisms that are swallowed in saliva, which explains the marked drop in microbial density between the
mouth and stomach in Figure 5.1. Loss of gastric acidity leads to colonization of the stomach with microbes that are swallowed in
saliva. This may have little consequence in healthy subjects, who have harmless saprophytes in their saliva. However, critically ill
patients often have pathogenic Gram-negative bacilli in their saliva (described later), and colonization of the stomach with these
pathogens can promote Gram-negative septicemia (from translocation across the gastric mucosa) (15), as well as lung infections
(from aspiration of infected gastric secretions into the airways) (16).

The antiseptic benefits of gastric acid will resurface in the next section.

Stress-related mucosal injury is a term used to describe erosions in the gastric mucosa that occur in almost all patients with acute, life-
threatening illness (18,19). These erosions can be superficial and confined to the mucosa, or they can bore deeper and extend into the
submucosa. The deeper lesions are called stress ulcers, and are more likely to cause troublesome bleeding. For the remainder of this
chapter, the term “stress ulcer” will indicate both types of gastric erosions.

The gastric mucosa must protect itself against injury from the acid environment in the stomach, and gastric mucosal blood flow is
considered to play an important part in this protection (by supplying nutrients to maintain the functional integrity of the mucosa). The
importance of mucosal blood flow is demonstrated by the fact that 70 to 90% of the blood supply to the stomach is delivered to the
gastric mucosa (20). Splanchnic vasoconstriction and hypoperfusion is common in critically ill patients, and the resultant decrease in
gastric mucosal blood flow is considered the principal cause of gastric erosions (18–20). Once the gastric mucosa is disrupted, the
acidity in the gastric lumen can aggravate the surface lesions.

Table 5.1 Risk Factors for Stress Ulcer Bleeding

Clinical Consequences
Erosions are visible on luminal surface of the stomach in 75% to 100% of patients within 24 hours of admission to the ICU (19). These
lesions often ooze blood from eroding into superficial capillaries, but clinically significant bleeding (i.e., results in a significant drop in
blood pressure or a drop in hemoglobin >2 g/dL) is observed in less than 5% of ICU patients (18,19,21).

Risk Factors
The conditions that predispose to stress ulcer bleeding are listed in Table 5.1 (18,21). The independent risk factors (i.e., require no66485457-66485438

other risk factors to promote bleeding) include mechanical ventilation for longer than 48 hours, and a significant coagulopathy (i.e.,
platelets <50,000, INR>1.5, or activated PTT>twice control) (21). However, all of the conditions in Table 5.1 are indications for
prophylaxis to prevent stress ulcer bleeding.

Preventive Measures
The goal of prophylaxis for stress ulcers is not to prevent their appearance (since they appear almost immediately after ICU admission),
but to prevent clinically significant bleeding from these lesions. Surveys indicate that about 90% of ICU patients receive some form of
prophylaxis for stress ulcer bleeding (22), but this is excessive. Prophylaxis is primarily indicated for the conditions listed in Table 5.1 ,
and is especially important for patients who are ventilator-dependent for longer than 48 hours, or have a significant coagulopathy.

Table 5.2 Drugs Used for Prophylaxis of Stress Ulcer Bleeding

Methods of Prophylaxis
The principal method of prophylaxis for stress ulcer bleeding is to block the production of gastric acid using histamine type-2 receptor
antagonists or proton pump inhibitors, and maintain a pH≥4 in gastric aspirates. The other method of prophylaxis involves the use of a
cytoprotective agent (sucralfate) that protects damaged areas of the gastric mucosa without altering gastric acidity. The individual drugs
that are used for prophylaxis of stress ulcer bleeding are shown in Table 5.2.

1Histamine H2- Receptor Antagonists

Inhibition of gastric acid secretion with histamine H2-receptor antagonists (H2 blockers) is the most popular method of stress ulcer
prophylaxis (22). The drugs most frequently used for this purpose are ranitidine and famotidine; both drugs are typically given as an
intravenous bolus in the doses shown in Table 5.2 . Ranitidine is the most studied gastric acid–suppressing drug for stress ulcer
prophylaxis. A single 50 mg dose of ranitidine given as an IV bolus will reduce gastric acidity (pH>4) for 6–8 hrs. (24), so the typical
ranitidine dosing regimen is 50 mg IV every 8 hours. Famotidine has a longer duration of action; i.e., a single 20 mg dose of
famotidine given as an IV bolus will reduce gastric acidity (pH>4) for 10–15 hours (23), so the typical famotidine dosing regimen is 20
mg IV every 12 hours.

DOSE ADJUSTMENTS: Intravenous doses of famotidine