Question 1

College Answer

Answers should address more than just prevention of gastric erosions/stress ulceration.

Consideration should be given to other causes including patients with known gastro-oesophageal varices (where sclerotherapy/banding, beta-blockers and techniques to lower venous pressure, and avoidance of local trauma should be considered).

With regard to stress ulceration many strategies have been employed, and should be considered in a broad answer.  General resuscitation of patients, correction of coagulopathy, early enteral feeding and avoidance of precipitants (eg. NSAIDs) in patients at risk are assumed to be beneficial (but not well studied).  Prospective randomised trials have generally compared drug regimens (antacids vs sucralfate vs H2-blockers vs proton pump inhibitors).  Other agents include prostaglandin analogs. Controversy surrounds the issues of widespread use of prophylactic agents, value of drugs vs placebo, nosocomial infection rates, and cost-benefit analyses.

Discussion

"Critically evaluate" demands a certain degree of structure. Contrary to the college answer, banding and sclerotherapy are not usually preventative techniques. If one were to dedicate any time during this ten minute answer to varices and leaking AVMs, one may wish to be very brief about it, as the meat is clearly in gastric ulceration.

Introduction

Gastrointestinal bleeding in the critically ill patient may be due to a variety of causes; these include bleeding from stress ulceration, oesophageal varices, and colonic polyps. Exacerbating causes include antiplatelet and anticoagulant medications, as well as poor perfusion of gastrointestinal mucosa in the context of shock. Given that in the ICU GI bleeding is combined with a series of other major organ dysfunction syndromes, it tends to have a castarophic mortality rate and it is important to be able to protect at-risk patients from this complication.

Rationale

Options:

• Proton pump inhibitors
• Histamine receptor antagonists
• non-pharmacological management - protective role of enteral feeding

Advantages

• Decreased risk of gastrointestinal bleeding
• Decreased exposure to blood products, and the attendent risks thereof

Disadvantages

• Decreased gastric acidity, thus increased risk of non-sterile aspiration
• Increased risk of gastrointestinal bacterial overgrowth and translocation
• Increased risk of Clostridium difficile infections
• Economic disadvantage (cost)

Evidence for the routine use of ulcer prophylaxis

• A recent meta-analysis suggests that the quality and quantity of the evidence is still poor, but on the weight of the available evidence there is neither a mortality improvement nor any increase in the risk of nosocomial pneumonia.
• There appears to be no benefit for stress ulcer prophylaxis in patients who are tolerating enteral feeding, and in these patients stress ulcer prophylaxis is not needed.
• There is insufficent evidence to recommend the mandatory use of stress ulcer prophylaxis in any specific patient group (again, 
• Obviously, correcting coagulopathy (and not triggering any new coagulopathy, nor disabling the platelets with NSAIDs) is a good way to prevent catsatropic bleeding in the ICU.

Evidence to support one drug class over another

• At the time of this paper having been written, there was insufficient evidence to recommend any specific medication (e.e H₂As vs PPIs); however the Danes recommended PPIs, because they are more effective at keeping the gastric pH at over 4.0.
• There is now lots of evidence, and it is still unclear whether PPIs or H₂As are more effective. Pro-PPI studies include a big 2016 meta-analysis by Alshamsi et al, which revealed them to be more effective at preventing clinically significant episodes of bleeding. However, it must be pointed out that many of the studies which met inclusion criteria didn't even specify what they meant by "bleeding". When other meta-analysis authors selected studies  limited to ones with a low risk of bias, the results they arrived at were not significant (Barletta et al, 2016).

Summary

PPIs are indicated in at-risk patient in ICU who are intolerant of eneteral feeding, and who are otherwise at risk of gastrointestinal bleeding. Further research is required to discriminated between different classes of drugs in terms of efficacy, and to identify the at-risk population.

Steinberg, Kenneth P. "Stress-related mucosal disease in the critically ill patient: risk factors and strategies to prevent stress-related bleeding in the intensive care unit." Critical care medicine 30.6 (2002): S362-S364.

Marik, Paul E., et al. "Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis." Crit Care Med 38.11 (2010): 2222-2228.

Krag, Mette, et al. "Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients." Intensive care medicine 40.1 (2014): 11-22.

Madsen, Kristian Rørbæk, et al. "Guideline for Stress Ulcer Prophylaxis in the Intensive Care Unit." Danish medical journal 61.3 (2014): 1-4.

Alshamsi, Fayez, et al. "Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials." Critical Care 20.1 (2016): 120.

Barletta, Jeffrey F., et al. "Stress ulcer prophylaxis." Critical care medicine44.7 (2016): 1395-1405.