This chapter deals with protecting ICU patients from their own gastric secretions. This keeps appearing in the Second Part exam:
The issue of PPI prophylaxis was absent from the CICM Part II exam between 2003 and 2018. Because of this prolonged gap and because the content of assessment is the widely acknowledged driver for Part II revision, the modern-day candidates may not have been well-prepared for this topic. In order to attend to this shortcoming, this chapter has enjoyed an update to reflect contemporary data. It seems important, given that the college keeps asking about it, and some of the more influential examiners are also co-investigators of the Australian trials.
As far as published evidence goes, the time poor exam candidate would be wise to only choose one recent article and rely on it for all of their revision. Buendgens et al (2016) is a reasonable choice, as it is available for free.
The modern day day trainee, blinded by the limitations of their youth, may disregard this topic as something of trivial importance. The junior doctor in charge of recharting medications may view the prescription of "life-saving pantoprazole" as a mindless application of a poorly supported opinion-based department protocol. However, it is not so. Rather, the almost total eradication of significant stress ulceration from the ICUs of the modern era can mainly be attributed to the constant use of some sort of stress ulcer prophylaxis measures, even if these only consist of enteral nutrition.
Historically, this was a major issue. Lucas et al (1971) report a 5% rate of stress ulcer associated with such blood loss that mortality from these events was 80%; 100% of acute trauma patients had some sort of obvious ulceration on endoscopy. Of highly at-risk patients (respiratory failure multi-trauma etc) Hastings et al (1971) found a bleeding rate of around 25%. In short, without "life-saving pantoprazole" fully one quarter of your patients might end up having a serious GI haemorrhage.
Question 10 from the first paper of 2018 asked about this specifically, but five risk factoors would have only earned you 20% of the 10-mark SAQ. This makes sense because it would have been relatively easy to score full marks, because any damn thing will cause stress ulceration in the ICU. The gastric mucosa is like the canary in the coal mine, swooning at the first sign of any sort of calamity. According to Cook et al (1994) and Steinberg et al (2002), independent risk factors for stress ulceration are:
According to Buendgens et al (2016), a whole other range of lower-risk associations exist, which include:
So, virtually everybody in the ICU would qualify, according to these criteria. The perception that everybody is at risk has resulted in the use of PPI in about 80% of ICU patients. This makes some sense, because after three days of ICU stay we still see gastric erosions forming in about 90% of ICU patients, even in the modern era (Krag et al, 2016)
This is a topic of some debate.
It is thought that the gastric mucosa is a very energy-hungry organ. The process of maintaining a massive pH gradient and secreting all that mucus is in fact a very ATP-hungry process. The oxygen extraction ratio of the gastric mucosa must approach 100% at normal physiological conditions.
Thus any decrease in gastric blood flow would result in a diminished capacity to secrete this precious protective mucus. The result would be horrific. As the mucus dissipates, the gastric mucosa finds itself defenseless against the hideous environment of the gastric lumen, which by its hospitality resembles the atmosphere of Venus.
This is what people usually mean when they say "stress ulcer prrophylaxis". In order to protect the delicate gastric mucosa, one would want a slightly less acidic stomach. Thus, one ought to aim for a pH of around 3.5, roughly the same acidity as the inside of a grapefruit.
Even though this sounds sensible, nobody is entirely sure whether it works. Certainly the risk of gastric bleeding is reduced by this strategy, but there are other issues.
For instance, the alkaline environment of the stomach will now support the growth of oral bacteria, and thus expose the patient to the risk of ventilator-associated pneumonia. Not only aspiration is a concern - one study had linked the use of PPIs with a two-fold increase in the risk of C.difficile infection
Also, PPIs are not exactly benign drugs. Pantoprazole, for instance, can cause all sort of liver function abnormality. In short, it is no wonder that large scale studies of stress ulcer prophylaxis have not revealed any improvement in mortality. Some episodes of bleeding are prevented, to be sure - but some episodes of VAP may be created as a result, and ultimately a balance is achieved.
A recent meta-analysis suggests that the quality and quantity of the evidence for the use of stress ulcer prophylaxis is actually quite poor. There is neither a mortality improvement nor any increase in the risk of nosocomial pneumonia.
ADVANTAGES
DISADVANTAGES
The consensus is that it should be reserved for at-risk patients only.
There is no specific agent which has any obvious advantage.
There is no benefit for stress ulcer prophylaxis in patients who are tolerating enteral feeding.
Generally speaking, you have choice of four major drug classes:
Additionally, enteral nutrition could be viewed as a non-pharmacological form of stress ulcer prophylaxis.
Each class has its advantages and disadvantages. Question 10 from the first paper of 2018 also wanted the candidates to "include in your answer the available evidence for these"
There does not seem to be any agreement regarding which agent is best, if one were going to give stress ulcer prophylaxis. The Danes recommend PPIs, because they are more effective at keeping the gastric pH at over 4.0. Recent meta-analysis publications listed in Buendgens et al (2016) redemonstrated their superiority over antihistamines and the superiority of antihistamines over sucralfate.
For the purpose of answering an (unlikely) future question on this topic, the savvy candidate will have prepared a certain small volume of clever-sounding bullshit to discharge onto the exam paper. Such a volume is offered below, as response to a request to critically evaluate the strategies for prevention of gastrointestinal bleeding in the critically ill.
Introduction
Rationale and counter-rationale
Advantages
Disadvantages
Evidence for the routine use of ulcer prophylaxis
Evidence to support one drug class over another
Summary
PPIs are indicated in at-risk patient in ICU who are intolerant of enteral feeding, and who are otherwise at risk of gastrointestinal bleeding. H2 agonists may have a statistically insignificant significant mortality advantage over PPIs. Further research is required to identify the at-risk population.
Oh's Intensive Care manual: Chapter 42 (pp. 487) Acute gastrointestinal bleeding by Joseph JY Sung
Cook, Deborah J., et al. "Risk factors for gastrointestinal bleeding in critically ill patients." New England Journal of Medicine 330.6 (1994): 377-381.
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.
Plummer, Mark P., Annika Reintam Blaser, and Adam M. Deane. "Stress ulceration: prevalence, pathology and association with adverse outcomes."Critical Care 18.2 (2014): 213.
Yearsley, K. A., et al. "Proton pump inhibitor therapy is a risk factor for Clostridium difficile‐associated diarrhoea." Alimentary pharmacology & therapeutics 24.4 (2006): 613-619.
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.
Buendgens, Lukas, Alexander Koch, and Frank Tacke. "Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis." World journal of critical care medicine 5.1 (2016): 57.
Gonzalez, Edgar R., and Anthony R. Morkunas. "Prophylaxis of stress ulcers: Antacid titration vs. histamine2-receptor blockade." Drug intelligence & clinical pharmacy 19.11 (1985): 807-811.
Cook, Deborah, et al. "A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation." New England Journal of Medicine 338.12 (1998): 791-797.
Oh's Intensive Care manual: Chapter 42 (pp. 487) Acute gastrointestinal bleeding by Joseph JY Sung
Cook, Deborah J., et al. "Risk factors for gastrointestinal bleeding in critically ill patients." New England Journal of Medicine 330.6 (1994): 377-381.
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.
Plummer, Mark P., Annika Reintam Blaser, and Adam M. Deane. "Stress ulceration: prevalence, pathology and association with adverse outcomes."Critical Care 18.2 (2014): 213.
Yearsley, K. A., et al. "Proton pump inhibitor therapy is a risk factor for Clostridium difficile‐associated diarrhoea." Alimentary pharmacology & therapeutics 24.4 (2006): 613-619.
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.
Buendgens, Lukas, Alexander Koch, and Frank Tacke. "Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis." World journal of critical care medicine 5.1 (2016): 57.
Gonzalez, Edgar R., and Anthony R. Morkunas. "Prophylaxis of stress ulcers: Antacid titration vs. histamine2-receptor blockade." Drug intelligence & clinical pharmacy 19.11 (1985): 807-811.
Cook, Deborah, et al. "A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation." New England Journal of Medicine 338.12 (1998): 791-797.
MacLaren, Robert, Catherine L. Jarvis, and Douglas N. Fish. "Use of enteral nutrition for stress ulcer prophylaxis." Annals of Pharmacotherapy 35.12 (2001): 1614-1623.
El-Kersh, Karim, et al. "Enteral nutrition as stress ulcer prophylaxis in critically ill patients: A randomized controlled exploratory study." Journal of critical care 43 (2018): 108-113.
Alhazzani, Waleed, et al. "Withholding pantoprazole for stress ulcer prophylaxis in critically ill patients: a pilot randomized clinical trial and meta-analysis." Critical care medicine 45.7 (2017): 1121-1129.
Lucas, Charles E., et al. "Natural history and surgical dilemma of stress gastric bleeding." Archives of surgery 102.4 (1971): 266-273.
Hastings, Paul R., et al. "Antacid titration in the prevention of acute gastrointestinal bleeding: A controlled, randomized trial in 100 critically ill patients." New England Journal of Medicine298.19 (1978): 1041-1045.
Krag, Mette, et al. "Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial." Trials17.1 (2016): 205.
Krag, Mette, et al. "Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU." New England Journal of Medicine 379.23 (2018): 2199-2208.
Young, Paul J., et al. "Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital mortality among icu patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial." Jama 323.7 (2020): 616-626.