Intensive care unit stress ulcer prophylaxis: is it still needed?

Gastrointestinal bleeding is a major source of morbidity and is associated with a high mortality in patients who are critically ill and managed in the intensive care setting.1 Fortunately, the incidence of clinically significant gastrointestinal bleeding is much lower than initially anticipated. Nonetheless, an incidence of 1% is worth preventing.

The underlying cause of gastrointestinal bleeding in the intensive care unit (ICU) is attributed to stress related mucosal disease (SRMD). Interventions that can decrease the incidence include enteral nutrition and, currently the source of controversy, acid suppressive therapy. Stress ulcer bleeding prophylaxis has become the standard of care in ICUs despite the uncertainty in the timing of initiation,2 the most efficacious agent to be used, and lack of any proven effect on mortality.1,3

The use of these acid suppressive therapies is associated with some concerns like the potential association with nosocomial infections mainly ventilator-associated pneumonia, as well as Clostridium difficile infection, further adding to the general uncertainty about the cost-effectiveness of stress ulcer bleeding prophylaxis. Also, the target population that should receive prophylaxis has evolved from those that require prolonged ventilation, burns and head trauma to those with acute kidney injury, coagulopathy (platelet count <50 000/mL3, international normalized ratio >1.5, or partial-thromboplastin time more than two times the control value), and acute hepatic injury as well as those with chronic liver disease.1 Furthermore, the most cost-effective strategy for the prevention of gastrointestinal bleeding is controversial given the quality and size of these studies as well as the discrepancy in the variables included in calculating estimates.

The protocol for the pilot study Revaluating the Inhibition of Stress Erosions (REVISE) that is published in this issue of the Annals of Saudi Medicine thus comes at an important time. The protocol for a multicenter, international trial will attempt to control some of the sources of biases in prior published trials on SRMD prophylaxis. 4 It also comes at a time when current practice in the modern ICU includes early resuscitation and enteral nutrition, which is known to decrease SRMD; as such the current trial may be able to discern any added benefit attributable to stress ulcer bleeding prophylaxis.

Even though the proposal is that of a feasibility RCT with outcomes focusing on informed consent rate, recruitment rate, and protocol adherence, the plan is to pave the way for a more definitive study addressing clinically relevant patient outcomes.

The group is a highly respected team, known for their scientific rigour as demonstrated by explicit, improved definitions of various outcomes, including a clear distinction between clinically important and overt upper gastrointestinal bleeding, which has been more of an issue in prior trials.

The trial also puts into light some of the clinical controversies associated with the use of acid suppressive therapy; for example, the authors describe the detection of Clostridium difficile toxin in symptomatic patients while PCR is used in those who are asymptomatic. This might provide a better understanding of the natural history and effect of proton pump inhibitors on colonization as well as symptomatic rates of Clostridium difficile bacterium in this patient population.

Unfortunately, this trial will only focus on ventilated patients while other “at risk” patient populations will be excluded, such as patients with abnormal coagulation parameters or selected organ dysfunction; this will somewhat limit the generalizability of results. The use of acid suppressive therapy in these patients at high risk of developing SRMD is an important question that requires a better understanding. Also the authors excluded patients with a “poor prognosis” without using a better definition of this selection criterion, which could introduce some biases in patient selection. As the study is limited to patients who are ventilated, we are not sure how the authors anticipate recording an orthostatic increase in pulse rate or decrease in systolic blood pressure, which they have used in their definition of clinically important upper gastrointestinal bleeding. Whether this multicenter design will be taken into account in the economic evaluation of stress ulcer prophylaxis is not clear, but economic data collection (at least at some sites), possibly in the form of resource consumption, would be very informative for subsequent economic modeling and would complement the trial results.

In conclusion, the protocol for this proposed pilot international RCT will hopefully pave the way for a full RCT that will guide future practice and will either challenge or support current recommendations in stress ulcer prophylaxis in the ICU.