Algorithm based management improves compliance with Stress Ulcer Prophylaxis in ICU

Sanjay Deshpande, MA Dessoky and Peter Brock used algorithm to identify patients at risk with stress related mucosal disease, those with an indication for IV prophylaxis, and those with indications for Proton Pump Inhibitor (PPI) use.

Summary

Stress related mucosal disease could be seen in more than 75 per cent of patients in ICU, with less than 4 per cent developing significant GI bleeding. It is important to identify those at risk of GI bleeding and provide prophylaxis against this, while avoiding inappropriate blanket treatment of all ICU patients.

Using the American Society of Health-System Pharmacists guidelines, we evaluated an algorithm to identify patients at risk, those with an indication for IV prophylaxis, and those with indications for Proton Pump Inhibitor (PPI) use.

The proposed algorithm increased the compliance with the guidelines. After implementation of the algorithm based assessment 100 per cent of patients requiring prophylaxis received it, versus 96 per cent before the implementation, 66 per cent of patients not requiring prophylaxis didn’t receive it versus 33 per cent before. 88 per cent of patients requiring PPI prophylaxis received it versus 66 per cent before. 76 per cent of patients requiring IV prophylaxis received it, versus 66 per cent before.

To date few guidelines has been proposed for SUP of which ASHP guidelines still a valid and recommended one. The use of an algorithm based intervention for SUP improves the compliance with the guidelines in our unit.

 

Introduction:

Stress related mucosal disease could be seen on endoscopy in 75-100 per cent of patients within 24 hours of arrival to ICU [1]. However, only 0.1-4 per cent of ICU patients will develop clinically significant gastrointestinal (GI) bleeding [2]. Of those who do develop GI bleeding, mortality is significantly increased 48.5 per cent vs 9 per cent [3].

The American Society of Health-System Pharmacists “ASHP” published guidelines in 1999 for the use of Stress Ulcer Prophylaxis “SUP” in medical and surgical ICU patients. It identifies the risk factors associated with stress related mucosal disease. [4]

Therefore, it is important to identify those at risk of GI bleeding and provide prophylaxis against this – given the significant mortality related to a GI bleed. However, blanket treatment of all critically ill patients is not appropriate for a multitude of reasons.

Clearly cost is a factor. Intravenous proton pump inhibitor “PPI” preparations are expensive in comparison to H2 blockers. Also PPI is associated with increased risk of clostridium difficile infection. [15]

The algorithm, which we developed in our unit, prompts to consider prescribing stress ulcer prophylaxis for every patient on the unit. ICU doctor then reviews patients and makes a decision based on their judgement.

An audit of practice in comparison to current ASHP guidelines for prescription of stress ulcer prophylaxis in critical care patients was performed.

 

Methods:

Using the American Society of Health-System Pharmacists guidelines as a standard, we expected that all patients with risk factors (as defined by the ASHP guidelines) for clinically significant GI bleed should receive stress ulcer prophylaxis. Patients without risk factors for clinically significant GI bleed should not receive stress ulcer prophylaxis. Of the patients given stress ulcer prophylaxis, only those with indications for PPI should receive it, and of the patients given stress ulcer prophylaxis, only those with indications for IV use should receive IV medication.

35 critical care patients on our unit were audited between 1 August 2012 and 7 October 2012.

With no current prescribing algorithm for stress ulcer prophylaxis in place we proposed an algorithm (figure 1) to be adopted in our unit. This algorithm is based on the ASHP guidelines. It airs on the side of prescribing stress ulcer prophylaxis even in those with risk factors that the evidence base is relatively weak for.

Figure 1 Prescribing algorithm for stress ulcer prophylaxis in critical care patients.

 

We kept the prompt for stress ulcer prophylaxis on the ward round proforma, as it needs to be considered with every patient.

A post intervention audit was performed from 1 February 2013 to 8 May 2013 that included 39 patients. Same data collection method and audit criteria were applied.

 

Results:

First audit results:

We found that before the application of the algorithm suggested, 96 per cent of those who should have received prophylaxis did. Only 33 per cent of those patients who should have not been given stress ulcer prophylaxis had no stress ulcer prophylaxis prescribed to them. 66 per cent of the patients who received stress ulcer prophylaxis received the appropriate drug, with an over prescription of PPI therapy and its subsequent cost and side effect implications. 66 per cent of the patients who received stress ulcer prophylaxis received the drugs via the most appropriate route.

Second audit results:

After application of the algorithm, 100 per cent of patients who required SUP were given it (36 out of 36). 66 per cent of those who should not have received SUP managed appropriately (two out of three). 88 per cent of those with an indication for receiving a PPI received a PPI (15 out of 17). 83 per cent without indication for PPI were given H2 receptor antagonist (15 out of 18) and, 76 per cent without indication for IV treatment were given PO treatment (13 out of 17).

Discussion:

Acute upper gastrointestinal bleeding is a common condition that has an estimated annual incidence of 40 −150 cases per 100 000 population worldwide which leads to hospital admission, with significant associated morbidity and mortality [5,6]

Endoscopic studies in the 1970’s had shown that stress related mucosal disease could be seen in 75-100 per cent of patients within 24 hours of arrival to ITU [1,7]. However, only 0.1-4 per cent of ITU patients will develop clinically significant gastrointestinal (GI) bleeding [2]. This suggests that blanket treatment with potentially expensive pharmaceutical agents would be clinically and cost ineffective.

A recent multicentre study that included 1034 patients from 11 countries has found that GI bleeding occurred in 2.6 per cent, and the odds of mortality of those patients were high [8].

It is evident that of those who do develop GI bleeding, mortality is significantly increased 48.5 per cent vs. 9 per cent [3]. Therefore, prophylactic treatment to a high-risk group is likely to have clinical value.

This is why stress ulcer prophylaxis (SUP) is commonly used in the intensive care unit (ICU), and is recommended in the Surviving Sepsis Campaign guidelines 2012 [9].

Buckley et al [10] could show that 14.4 per cent of patients in an ICU received acid suppression without proper indication, which resulted in unnecessary risk of side effects and unnecessary costs (> 200,000 dollar annually in the study hospital). So it is mandatory to frequently re-evaluate the individual indication for SUP both during and after ICU [10].

Firstly to consider H2 receptor antagonists. Cook et al [11] conducted a meta-analysis that included 10 randomised clinical trials comparing H2 receptor antagonist therapy to placebo. They found H2 receptor antagonist therapy was superior to placebo in reducing the risk of clinically significant bleeds (odds ratio [OR], 0.44, 95 per cent confidence interval [CI], 0.22–0.88). This conclusion was supported by a systematic review [12] comparing H2 receptor antagonist with placebo and including 1836 patients from 17 randomised control trials (OR, 0.47; 95 per cent CI, 0.29–0.76; P <0.002).

PPI therapy has been shown to be equally efficacious, but not superior. Lin et al [13] produced a meta-analysis including 936 patients from seven RCTs and reported no difference in the rate of CIB between PPI and H2 receptor antagonist (risk difference of 0.04; 95 per cent CI, –0.09 to 0.01; P = 0.08). It has shown that the efficacy and safety of proton pump inhibitors was not significantly different to H2 receptor antagonists in terms of stress related upper GI bleeding and mortality [13]. However, this only included 7 trials, which varied in patient inclusion criteria, agents used, doses and route of administration. The authors themselves concluded that due to limited trial data the evidence remains inconclusive and well powered future randomised control trials are needed, with which the authors would concur. Therefore, at present with no significant evidence to suggest that PPIs are better than H2 receptor antagonists, it would be prudent to use H2 receptor antagonists as a first line therapy due to cost implications.

Proton pump inhibitors were more effective than histamine 2 receptor antagonists at reducing clinically important upper gastrointestinal bleeding [14] PPI was associated with increased incidence of Clostridium Dificile associated diarrhoea [15]. Studies showed that PPI use was an independent predictor of mortality [16].

Again there is a lack of evidence in the area of the effectiveness of differing routes of administration of each agent specifically in the setting of stress ulcer prophylaxis. Literature, which suggests that there, is no added efficacy or safety in using intravenous stress ulcer prophylaxis over enteral stress ulcer prophylaxis [17]. In addition, in the meta-analysis regarding PPI vs. H2 receptor antagonist described above [13] only three of the trials has an enteral route of SUP administration. Therefore, with the exception of caveats such as post endoscopy PPI infusions [18], if deemed that the patient is able to swallow, or if no concerns have been raised regarding the absorption of NG fluids or feeds then the PO/NG route should be used when possible.

In early 1994, risk factors for GI bleeding in critical care were first assessed [4] Since then, several studies have been undertaken to determine risk factors of clinically significant GI bleeds in the ITU, with the latest guidelines coming from the American Society of Health-System Pharmacists (ASHP) in 1999. These guidelines state a relatively specific set of appropriate indications for instigation of stress ulcer prophylaxis in critically ill patients (Table 1).

This inclusion criterion however should be broached with caution. The level of evidence used by the authors is at times relatively low, although obviously the ethical difficulties in performing a true placebo controlled randomised control trials would be ethically difficult to justify. The guidelines are also over 15 years old and it appears from literature search that in this period, there has been a relative paucity of high quality new risk stratification data. Therefore, although these guidelines remain the most commonly accepted guidelines used in clinical and academic practice they are not without some limitation.

Seven clinical guidelines for SUP were appraised using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument from 1999 to 2014. ASHP guidelines had high clarity of presentation, highest stakeholder involvements, and highest applicability [19].

Other algorithms for stress ulcer prophylaxis were proposed, for the different indications for SUP based on other guidelines [20].

Our proposed algorithm is based heavily on the American Society of Health-System Pharmacists guidelines. It is a conservative one, and errs on the side of prescribing stress ulcer prophylaxis even in those with risk factors that the evidence base is relatively weak for. We have tailored the algorithm to include not only the indications for SUP, but also have included the indications for PPI and the route preference. Which makes this algorithm comprehensive.

We have shown that using such a comprehensive algorithm leads to better compliance to the guidelines, with the end result of better patient outcome and cost-effectiveness.

 

Conclusion:

To date few guidelines have been proposed for SUP of which ASHP guidelines still a valid and recommended one.

The use of an algorithm based intervention for SUP improves the compliance with the guidelines in our unit.

 

 

Authors:

Sanjay Deshpande, Anaesthesia Consultant, STFT South Tyneside Hospital, South Shields, United Kingdom, Sanjay.deshpande@stft.nhs.uk

MA Dessoky, Anaesthesia speciality doctor, North Tees and Hartlepool TRUST, Stockton-on-Tees, United Kingdom, Maed1978@gmail.com

Peter Brock, Specialist Trainee Geriatrics, Northumbria Healthcare NHS Foundation Trust, peter.brock@nhs.net

 

Acknowledgments: Nothing to acknowledge

Competing interests: No external funding and no competing interests declared

Peer reviewed by Nitin Arora

 

References

1. Lucas CE, Sugawa C, Riddle J, et al. Natural history and surgical dilemma of “stress” gastric bleeding. Arch Surg. 1971; 102: 266:273
2. Fennerty MB. Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. Crit care Med 2002; 30:S351-S355
3. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994; 330: 377:381
4. ASHP Therapeutic Guidelines on stress ulcer prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm 1999; 56: 347-379
5. Van Leerdam ME. Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol 2008; 22: 209-224
6. Hearnshaw SA, Logan RF, Lowe D et al. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut 2011; 60: 1327-1335
7. Czaja AJ, McAlhany JC, Pruitt BA Jr. Acute gastroduodenal disease after thermal injury. An endoscopic evaluation of incidence and natural history. N Engl J Med. 1974; 291: 925:929
8. Krag M, Perner A, Wetterslev J, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients.Intensive Care Med. 2015 May;41(5):833-45.
9. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign Guidelines Committee including the Paediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb; 41(2): 580-637.
10. Buckley MS, Park AS, Anderson CS, et al. Impact of a clinical pharmacist stress ulcer prophylaxis management program on inappropriate use in hospitalized patients. Am J Med. 2015; 128:905–913.
11. Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta‑ JAMA. 1996; 275: 308:314.
12. Marik PE, Vasu T, Hirani A, Pachinburavan M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med. 2010; 38: 2222:2228.
13. Lin PC, Change CH et al. The efficacy and safety of proton pump inhibitors vs. histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among crtical care patients: A meta-analysis. Crit Care Med 2010. Vol. 38, No 4, 1197:1205
14. Alhazzani W, Alenezi F, Jaeschke RZ, Moayyedi P, Cook DJ.Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis.
    Crit Care Med. 2013 Mar; 41(3): 693-705.
15. Buendgens L1, Bruensing J1, Matthes M1, Dückers H1, Luedde T1, Trautwein C1, Tacke F2, Koch A1. Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea. J Crit Care. 2014 Aug; 29(4): 696.e11–696.e15
16. Dultz G1, Piiper A, Zeuzem S, Kronenberger B, Waidmann O. Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis.Aliment Pharmacol Ther. 2015 Mar; 41(5): 459-66.
17. Impact of trauma stress ulcer prophylaxis guidelines on drug cost and frequency of major gastrointestinal bleeding. Devlin JW1, Claire KS, Dulchavsky SA, Tyburski JG. 1999 Apr; 19(4): 452-60.
18. Lanas A, Artal A, Blás JM, Arroyo MT, Lopez-Zaborras J, Sáinz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol. 1995; 21(2): 103:106
19. Critical Appraisal of the Quality of Clinical Practice Guidelines for Stress Ulcer Prophylaxis. Zhi-Kang Ye, Ying Liu, Xiang-Li Cui, Li-Hong Liu
    Published: May 6, 2016 http://dx.doi.org/10.1371/journal.pone.0155020
20. Lukas Buendgens, Alexander Koch, and Frank Tacke. Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis. World J Crit Care Med. 2016 Feb 4; 5(1): 57–64.